Submit to Biology Review for Biology Propose a Special Issue

Journal Browser

► Journal Browser

Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 22740

Share This Special Issue

Special Issue Editors

Prof. Dr. Simona Zaami

E-Mail Website
Guest Editor

Department of Anatomical, Histological, Forensic and Orthopedic Sciences, “Sapienza” University of Rome, 00161 Rome, Italy
Interests: public health; obstetrics/gynecology; oncology; oncofertility; bioethics; beginning-of life ethics; Assisted Reproductive Technologies (ART); genome Editing; non-coding RNAs as prognostic markers; forensic toxicology; new psychoactive substances; pharmacology; forensic psychiatry; neuroscience

Dr. Enrico Marinelli

E-Mail Website
Guest Editor

Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Sapienza University of Rome, 00185 Rome, Italy
Interests: legal medicine; clinical and forensic toxicology; insurance medicine; bioethics

Dr. Roberta Pacifici

E-Mail Website
Guest Editor

National Centre on Addiction and Doping, Istituto Superiore di Sanità, 00161 Rome, Italy
Interests: Pharmacotoxicology and epidemiology of psychotropic drugs and doping agents

Prof. Dr. Raffaele Giorgetti

E-Mail Website
Guest Editor

Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60121 Ancona, Italy
Interests: legal medicine; clinical and forensic toxicology; insurance medicine; bioethics

Dr. Simona Pichini

E-Mail Website
Guest Editor

National Centre on Addiction and Doping, National Institute of Health, 00161 Rome, Italy
Interests: clinical pharmacotoxicology; forensic pharmacotoxicology; psychoactive substances; doping agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to launch a Special Issue focusing on the determination of biomarkers of exposure to psychoactive substances.

Analytical evidence of human exposure to psychotropic substances often depends on the detectability of those molecules and/or their metabolites in biological matrices. After absorption, xenobiotics enter the blood to reach the molecular target through the circulatory system where they can exert their effects.

In the past century, the presence and disposition of a drug inside the human body and eventual association with clinical/subjective effects had been mainly detected by blood and urine testing, since it was not always possible or desirable (because it was difficult and/or invasive) to sample other biological matrices and fluids. Nonetheless, the measurement of drug concentration in fluids and matrices other than blood and urine (the so-called “nonconventional fluids and matrices”) has gained increasing importance. First of all, improved technology (noninvasive sample collection, dedicated devices for sample collection, different possibilities of extraction procedures, and new-generation analytical instrumentation) has made the measurement of minute quantities of parent substances and/or metabolites extracted from complex biological matrices possible. Secondly, it appears that the determination of drug and/or metabolite concentrations in nonconventional human body materials may be useful for two principal applications: firstly, the possibility of determining pharmacokinetic parameters at the target organ and target concentration intervention; and secondly, the expansion of drug detection window obtaining information on past and possible long-term exposure.

Since, before being eliminated, drugs undergo phase I and phase II metabolism, biomarkers of exposure to those substances are usually one or more metabolites, and their analytical characterization plays an essential role in the objective assessment of exposure to psychotropic substances.

In this Special Issue, attention will be focused on the analytical challenges posed by the characterization and determination of the most effective biomarkers of traditional and new psychoactive substances, within the framework of clinical and forensic toxicology.

Prof. Simona Zaami
Dr. Enrico Marinelli
Dr. Roberta Pacifici
Prof. Raffaele Giorgetti
Dr. Simona Pichini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

biomarkers
human
psychoactive substances
pharmacotoxicology
biological matrices
analytical methods

Published Papers (7 papers)

Download All Papers

Research

Jump to: Other

9 pages, 517 KiB

Open AccessArticle

Quantification of Carbonic Anhydrase Inhibitors and Metabolites in Urine and Hair of Patients and Their Relatives

by Alfredo Fabrizio Lo Faro, Anastasio Tini, Giulia Bambagiotti, Filippo Pirani, Andrea Faragalli, Flavia Carle, Elena Pacella, Artan Ceka, Marco Moretti, Massimo Gottardi, Nicola Vito Lassandro, Michele Nicolai, Marco Lupidi, Cesare Mariotti, Francesco Paolo Busardò and Jeremy Carlier

Biology 2022, 11(10), 1379; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11101379 - 21 Sep 2022

Cited by 2 | Viewed by 1723

Abstract

Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients’ relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 μL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2–501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9–125.3 ng/mL) for N-deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL–0.84 ng/mL) for N-acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4–79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7–437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1–0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06–0.08 ng/mg) for N-deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13–1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

► Show Figures

Figure 1

9 pages, 283 KiB

Open AccessArticle

New Psychoactive Substances Consumption in Opioid-Use Disorder Patients

by Maria Alías-Ferri, Manuela Pellegrini, Emilia Marchei, Roberta Pacifici, Maria Concetta Rotolo, Simona Pichini, Clara Pérez-Mañá, Esther Papaseit, Robert Muga, Francina Fonseca, Marta Torrens and Magí Farré

Biology 2022, 11(5), 645; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11050645 - 22 Apr 2022

Cited by 3 | Viewed by 2267

Abstract

(1) Background: Since the beginning of the 21st century, the large number and wide chemical variety of new psychoactive substances (NPS) that enter the market every year has become a public health problem. Given the rapidity with which the drug market is changing, many NPS are not clinically investigated and their effects and health risks are unknown. Drug testing is a very useful tool for this purpose, but, unfortunately, it is not very widespread in individuals with opioid-use disorder under detoxification treatment. The aim of this study is to investigate the use of illicit drugs and NPS in opioid-use disorder (OUD) patients on opioid agonist treatment. (2) Methods: A multicenter, descriptive, cross-sectional study was conducted at two addiction care services in Barcelona and Badalona, Spain. Urine samples were collected from OUD individuals attending these two centers, who anonymously donated a urine sample at the time of a periodical visit. Samples were analyzed by high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high –resolution mass spectrometry (UHPLC-HRMS). (3) Results: Out of the 187 collected and analyzed urine samples, 27.3% were positive for any type of NPS and 8.6% were positive for new synthetic opioids, including fentanyl and its derivatives (NSO). Other frequently detected substances were benzodiazepines in 46.0% of samples, antipsychotics in 27.8% of samples, or cocaine and cannabis in 23.5% of samples. (4) Conclusion: A wide number of NPS, including NSO, have been detected in urine samples from an OUD population. A lack of NPS detection in standard drug screening among drug users can hide the identification of a potential public health problem. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

16 pages, 1150 KiB

Open AccessArticle

A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure

by Lourdes Poyatos, Esther Papaseit, Eulalia Olesti, Clara Pérez-Mañá, Mireia Ventura, Xoán Carbón, Marc Grifell, Francina Fonseca, Marta Torrens, Rafael de la Torre and Magí Farré

Biology 2021, 10(8), 788; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10080788 - 17 Aug 2021

Cited by 10 | Viewed by 4102

Abstract

Considered the β-keto analogue of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-Methylenedioxymethcathinone (methylone) is a synthetic cathinone. Over the years, methylone has been used as a substitute for conventional psychostimulants, such as MDMA. To date, little is known about the human pharmacology of methylone; the only available information has been provided by surveys or published intoxication reports. In the present observational–naturalistic study, we evaluate the acute subjective and physiological effects of methylone after oral self-administration in comparison to MDMA in healthy poly-drug users. Fourteen participants (10 males, 4 females) selected their single oral doses of methylone from 100 to 300 mg (n = 8, mean dose 187.5 mg) or MDMA from 75 to 100 mg (n = 6, mean dose 87.5 mg) based on their experience. Study variables were assessed at 0, 1, 2, and 4 h (h) and included vital signs (non-invasive blood pressure, heart rate, cutaneous temperature) and subjective effects using visual analogue scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI) short form, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) questionnaire. Additionally, oral fluid concentrations of methylone and MDMA were determined. Acute pharmacological effects produced by methylone followed the prototypical psychostimulant and empathogenic profile associated with MDMA, although they were less intense. Methylone concentrations in oral fluid can be considered a useful biomarker to detect acute exposure in oral fluid. Oral fluid concentrations of MDMA and methylone peaked at 2 h and concentrations of MDMA were in the range of those previously described in controlled studies. Our results demonstrate that the potential abuse liability of methylone is similar to that of MDMA in recreational subjects. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

► Show Figures

Figure 1

9 pages, 279 KiB

Open AccessEditor’s ChoiceArticle

Hair Testing for Classic Drugs of Abuse to Monitor Cocaine Use Disorder in Patients Following Transcranial Magnetic Stimulation Protocol Treatment

by Maria Concetta Rotolo, Roberta Pacifici, Manuela Pellegrini, Stefano Cardullo, Luis J. Gómez Pérez, Diego Cuppone, Luigi Gallimberti and Graziella Madeo

Biology 2021, 10(5), 403; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10050403 - 05 May 2021

Cited by 8 | Viewed by 3748

Abstract

In recent years, hair has become an alternative biological specimen for drug testing in the fields of forensic and clinical toxicology. The advantages of hair testing include larger detection windows (months/years), depending on the length of the hair shaft, compared to those of urine/blood (hours to 2–4 days for most drugs). Segmental hair analysis can disclose a month-to-month (considering 1 cm segment cuts) information of drug exposure (single or repeated) and potentially identify patterns of drug use/administration. Repetitive transcranial magnetic stimulation (rTMS) was recently proposed as a valid tool for therapeutic purposes in addictions, including cocaine use disorder (CocUD). Here, we proposed hair testing analyses of classic drugs of abuse in a clinical setting to monitor the clinical changes in treatment-seeker CocUD patients undergoing protocol treatments with rTMS stimulating the left dorsolateral prefrontal cortex (l-DLPFC). We collected hair samples from nine CocUD patients at different stages from the beginning of treatments. Hair sample analyses revealed significant changes in the patterns of cocaine use, according to the negativity of urine screening tests and the clinical reductions of craving. These data, albeit preliminary, suggest that hair testing analysis of classic drugs of abuse could be extended to clinical settings to monitor the clinical efficacy of innovative therapeutic interventions, such as rTMS. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

15 pages, 848 KiB

Open AccessArticle

Role of Neonatal Biomarkers of Exposure to Psychoactive Substances to Identify Maternal Socio-Demographic Determinants

by Pilar Jarque, Antonia Roca, Isabel Gomila, Emilia Marchei, Roberta Tittarelli, Miguel Ángel Elorza, Pilar Sanchís and Bernardino Barceló

Biology 2021, 10(4), 296; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10040296 - 04 Apr 2021

Cited by 3 | Viewed by 2293

Abstract

Background: The accurate assessment of fetal exposure to psychoactive substances provides the basis for appropriate clinical care of neonates. The objective of this study was to identify maternal socio-demographic profiles and risk factors for prenatal exposure to drugs of abuse by measuring biomarkers in neonatal matrices. Methods: A prospective, observational cohort study was completed. Biomarkers of fetal exposure were measured in meconium samples. The mothers were interviewed using a questionnaire. Univariate and multivariate logistic regression analyses were performed. Results: A total of 372 mothers were included, 49 (13.2%) testing positive for psychoactive substances use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and in eight (16.3%) more than one psychoactive substance. Mothers who consumed any psychoactive substance (29.7 ± 6.6 years) or cannabis (27.0 ± 5.7 years) were younger than non-users (32.8 ± 6.2 years, p < 0.05). Cocaine (50.0% vs. 96.9%, p < 0.05) and polydrug users (37.5% vs. 96.9%, p < 0.05) showed a lower levels of pregnancy care. Previous abortions were associated with the use of two or more psychoactive substances (87.5% vs. 37.8%, p < 0.05). Single-mother families (14.3% vs. 2.5%, p < 0.05) and mothers with primary level education (75.5% vs. 55.1%, p < 0.05) presented a higher consumption of psychoactive substances. Independent risk factors that are associated with prenatal exposure include: maternal age < 24 years (odds ratio: 2.56; 95% CI: 1.12–5.87), lack of pregnancy care (odds ratio: 7.27; 95%CI: 2.51–21.02), single-mother families (odds ratio: 4.98; 95%CI: 1.37–8.13), and active tobacco smoking (odds ratio: 8.13; 95%CI: 4.03–16.43). Conclusions: These results will allow us to develop several risk-based drug screening approaches to improve the early detection of exposed neonates. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

► Show Figures

Figure 1

14 pages, 991 KiB

Open AccessArticle

Acute Pharmacological Effects and Oral Fluid Biomarkers of the Synthetic Cannabinoid UR-144 and THC in Recreational Users

by Nunzia La Maida, Esther Papaseit, Lucia Martínez, Clara Pérez-Mañá, Lourdes Poyatos, Manuela Pellegrini, Simona Pichini, Roberta Pacifici, Mireia Ventura, Liliana Galindo, Francesco Paolo Busardò and Magí Farré

Biology 2021, 10(4), 257; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10040257 - 24 Mar 2021

Cited by 11 | Viewed by 3827

Abstract

Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

► Show Figures

Figure 1

Other

Jump to: Research

24 pages, 2787 KiB

Open AccessSystematic Review

Detection of the Synthetic Cannabinoids AB-CHMINACA, ADB-CHMINACA, MDMB-CHMICA, and 5F-MDMB-PINACA in Biological Matrices: A Systematic Review

by Elisabet Navarro-Tapia, Jana Codina, Víctor José Villanueva-Blasco, Óscar García-Algar and Vicente Andreu-Fernández

Biology 2022, 11(5), 796; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11050796 - 23 May 2022

Cited by 6 | Viewed by 3507

Abstract

New synthetic cannabinoids (SCs) are emerging rapidly and continuously. Biological matrices are key for their precise detection to link toxicity and symptoms to each compound and concentration and ascertain consumption trends. The objective of this study was to determine the best human biological matrices to detect the risk-assessed compounds provided by The European Monitoring Centre for Drugs and Drug Addiction: AB-CHMINACA, ADB-CHMNACA, MDMB-CHMICA, and 5F-MDMB-PINACA. We carried out a systematic review covering 2015 up to the present date, including original articles assessing detection in antemortem human biological matrices with detailed validation information of the technique. In oral fluid and blood, SC parent compounds were found in oral fluid and blood at low concentrations and usually with other substances; thus, the correlation between SCs concentrations and severity of symptoms could rarely be established. When hair is used as the biological matrix, there are difficulties in excluding passive contamination when evaluating chronic consumption. Detection of metabolites in urine is complex because it requires prior identification studies. LC-MS/MS assays were the most widely used approaches for the selective identification of SCs, although the lack of standard references and the need for revalidation with the continuous emergence of new SCs are limiting factors of this technique. A potential solution is high-resolution mass spectrometry screening, which allows for non-targeted detection and retrospective data interrogation. Full article

(This article belongs to the Special Issue Last Updates on Biomarkers of Exposure to Psychoactive Substances in Humans)

► Show Figures