Exploring the Potential Impact of GLP-1 Receptor Agonists on Substance Use, Compulsive Behavior, and Libido: Insights from Social Media Using a Mixed-Methods Approach.

Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on substance and behavioral addictions, including alcohol, caffeine, nicotine, cannabis, psychostimulants, compulsive shopping, and sex drive/libido. Data were collected from various social platforms. Keywords related to GLP-1 RAs and substance/behavioral addiction were used to extract relevant comments. The study employed a mixed-methods approach to analyze online discussions posted from December 2019 to June 2023 and collected using a specialized web application. Reddit entries were the focus here due to limited data from other platforms, such as TikTok and YouTube. A total of 5859 threads and related comments were extracted from six subreddits, which included threads about GLP-1 RAs drugs and associated brand names. To obtain relevant posts, keywords related to potential substance use and compulsive behavior were selected. Further analysis involved two main steps: (1) manually coding posts based on users' references to the potential impact of GLP-1 RAs on substance use and non-substance habits, excluding irrelevant or unclear comments; (2) performing a thematic analysis on the dataset of keywords, using AI-assisted techniques followed by the manual revision of the generated themes. Second, a thematic analysis was performed on the keyword-related dataset, using AI-assisted techniques followed by the manual revision of the generated themes. In total, 29.75% of alcohol-related; 22.22% of caffeine-related; and 23.08% of nicotine-related comments clearly stated a cessation of the intake of these substances following the start of GLP-1 RAs prescription. Conversely, mixed results were found for cannabis intake, and only limited, anecdotal data were made available for cocaine, entactogens, and dissociative drugs' misuse. Regarding behavioral addictions, 21.35% of comments reported a compulsive shopping interruption, whilst the sexual drive/libido elements reportedly increased in several users. The current mixed-methods approach appeared to be a useful tool in gaining insight into complex topics such as the effects of GLP-1 RAs on substance and non-substance addiction-related disorders; some GLP-1 RA-related mental health benefits could also be inferred from here. Overall, it appeared that GLP-1 RAs may show the potential to target both substance craving and maladaptive/addictive behaviors, although further empirical research is needed.

New trends of drug abuse in custodial settings: A systematic review on the misuse of over-the-counter drugs, prescription-only-medications, and new psychoactive substances.

The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes.

Benzodiazepine Boom: Tracking Etizolam, Pyrazolam, and Flubromazepam from Pre-UK Psychoactive Act 2016 to Present Using Analytical and Social Listening Techniques.

INTRODUCTION: The designer benzodiazepine (DBZD) market continues to expand whilst evading regulatory controls. The widespread adoption of social media by pro-drug use communities encourages positive discussions around DBZD use/misuse, driving demand. This research addresses the evolution of three popular DBZDs, etizolam (E), flubromazepam (F), and pyrazolam (P), available on the drug market for over a decade, comparing the quantitative chemical analyses of tablet samples, purchased from the internet prior to the implementation of the Psychoactive Substances Act UK 2016, with the thematic netnographic analyses of social media content. METHOD: Drug samples were purchased from the internet in early 2016. The characterisation of all drug batches were performed using UHPLC-MS and supported with 1H NMR. In addition, netnographic studies across the platforms X (formerly Twitter) and Reddit, between 2016-2023, were conducted. The latter was supported by both manual and artificial intelligence (AI)-driven thematic analyses, using numerous.ai and ChatGPT, of social media threads and discussions. RESULTS: UHPLC-MS confirmed the expected drug in every sample, showing remarkable inter/intra batch variability across all batches (E = 13.8 ± 0.6 to 24.7 ± 0.9 mg; F = 4.0 ± 0.2 to 23.5 ± 0.8 mg; P = 5.2 ± 0.2 to 11.5 ± 0.4 mg). 1H NMR could not confirm etizolam as a lone compound in any etizolam batch. Thematic analyses showed etizolam dominated social media discussions (59% of all posts), with 24.2% of posts involving sale/purchase and 17.8% detailing new administration trends/poly-drug use scenarios. Artificial intelligence confirmed three of the top five trends identified manually. CONCLUSIONS: Purity variability identified across all tested samples emphasises the increased potential health risks associated with DBZD consumption. We propose the global DBZD market is exacerbated by surface web social media discussions, recorded across X and Reddit. Despite the appearance of newer analogues, these three DBZDs remain prevalent and popularised. Reporting themes on harm/effects and new developments in poly-drug use trends, demand for DBZDs continues to grow, despite their potent nature and potential risk to life. It is proposed that greater controls and constant live monitoring of social media user content is warranted to drive active regulation strategies and targeted, effective, harm reduction strategies.

Exploring the understanding, source of availability and level of access of cognitive enhancers among university students in the United Arab Emirates: A qualitative study.

OBJECTIVE: The use of prescription stimulants for cognitive enhancement by healthy university students, identified as the largest cohort of cognitive enhancer (CE) users, is of growing interest. The purpose of this study was to look at the understanding, perception, experience, and level of access of CEs among healthy university students in the United Arab Emirates (UAE). METHODS: The study was conducted in six highly competitive university programmes. Semi-structured interviews were conducted with 18 university students to discuss their own experiences and those of their friends and peers regarding the use of prescription stimulants. In addition, semi-structured interviews were conducted with seven teaching faculty staff members (registered pharmacists and medical doctors) to explore their views on the use of CEs in their university. RESULTS: Data were analysed thematically for the identification of themes and subthemes within the data using coding. It was found that, 'Adderall' was the most common prescribed CE drug and caffeine super strength pills were the most common non-prescribed CE drug, both reported to enhance concentration, motivation, and meet academic deadlines. CONCLUSIONS: It is expected that the findings of this study will be of interest to a wide range of services in UAE universities. This will enable them to raise awareness about the use of CEs among students.

GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach.

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms' users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has contributed to an ongoing worldwide shortage of the drug associated with levels of non-prescribed semaglutide intake. Furthermore, recent reports emphasized some GLP-1 RA-associated risks of triggering depression and suicidal thoughts. Consistent with the above, we aimed to assess the possible impact of GLP-1 RAs on mental health as being perceived and discussed in popular open platforms with the help of a mixed-methods approach. Reddit posts yielded 12,136 comments, YouTube videos 14,515, and TikTok videos 17,059, respectively. Out of these posts/entries, most represented matches related to sleep-related issues, including insomnia (n = 620 matches); anxiety (n = 353); depression (n = 204); and mental health issues in general (n = 165). After the initiation of GLP-1 RAs, losing weight was associated with either a marked improvement or, in some cases, a deterioration, in mood; increase/decrease in anxiety/insomnia; and better control of a range of addictive behaviors. The challenges of accessing these medications were a hot topic as well. To the best of our knowledge, this is the first study documenting if and how GLP-1 RAs are perceived as affecting mood, mental health, and behaviors. Establishing a clear cause-and-effect link between metabolic diseases, depression and medications is difficult because of their possible reciprocal relationship, shared underlying mechanisms and individual differences. Further research is needed to better understand the safety profile of these molecules and their putative impact on behavioral and non-behavioral addictions.

Experience and views of healthcare professionals towards people who use new psychoactive substances: Evidence from statutory, non-statutory, and private mental health and addiction healthcare services.

OBJECTIVE: It is unclear how healthcare professionals (HCPs) experience and view the challenges of working with people who use New Psychoactive Substances (PWUNPS), in different healthcare services (HCS). The aim of the study was to explore HCPs' experiences of working with individuals who use NPS across statutory, non-statutory, and private mental health and addiction HCSs. METHODS: HCPs completed in-depth semi-structured interviews. Audio recordings were transcribed verbatim with a mean duration of 30 min 55 s. Data were analysed through thematic analysis. RESULTS: A purposive sample of 14 HCPs (6 men, 8 women) with a mean age of 42.5 years were interviewed in 2019. Organisational issues, including funding, impacted the treatment for PWUNPS and HCPs perceived a lack of support dependent on their qualifications. They reported a lack of assessment, policy, harm reduction, and awareness of NPS-related symptoms including mental health problems and stigma faced by PWUNPS. CONCLUSION: HCPs need better training, education, and assessment processes to manage acute NPS intoxications and address the stigma associated with PWUNPS. There is a need for policy-making opportunities across different HCSs to ensure better healthcare outcomes for PWUNPS.

Obstacles to treatment retention in opioid use disorder: An international substance use disorder treatment worker survey.

INTRODUCTION: Treatment retention is associated with better outcomes and reduced risk amongst people experiencing opioid use disorder (OUD). Despite this, treatment retention remains low amongst this population. METHODS: We carried out an international cross-sectional survey of substance use disorder (SUD) treatment service workers. We aimed to understand the barriers to treatment retention in the context of OUD from the provider perspective, identify differences in response preference between professional groups, and describe regional differences in treatment provision. RESULTS: We report data from 497 respondents based in the USA and the UK. Personality disorders, low motivation to change and social problems were the most often reported obstacles to retention. Comorbid SUD, hepatitis and HIV were not reported as often as expected. We identified associations between professional groups and response preferences related to comorbid SUD, low motivation, living arrangements and communication difficulties. UK respondents used behavioural treatments more than their US counterparts. US respondents more often reported using objective methods of measuring retention such as urine analysis, compared to their UK counterparts. DISCUSSION: The findings from this survey suggest that regional differences exist between US and UK based SUD treatment service workers. Personality disorders represented the most often experienced obstacles to treatment retention amongst patients with OUD, with mental health and social problems more often reported than comorbid drug problems or physical health problems. Statistically significant relationships exist between professional group and obstacles reported. These data may be used to identify additional training needs amongst SUD treatment service staff.

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset.

Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine-topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs 'drug abuse', 'drug withdrawal syndrome', 'prescription drug used without a prescription', and 'intentional product use issue' were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Handheld Raman Spectroscopy in the First UK Home Office Licensed Pharmacist-Led Community Drug Checking Service.

Across the world, the interest in point-of-care drug checking as a harm-reduction intervention is growing. This is an attempt to improve intelligence about current drug trends and reduce drug-related morbidity and mortality. In the UK, drug-related harm is increasing exponentially year after year. As such, specialist community treatment services are exploring new methods to improve engagement with people who use drugs (PWUD), who may require support for their problematic drug use. This need has driven the requirement to pilot an on-site, time-responsive, readily available drug-checking service at point-of-support centres. In this study, we piloted the UK's first Home Office-licensed drug-checking service that was embedded into a community substance-misuse service and had all on-site analysis and harm-reduction interventions led and delivered by pharmacists. We report on the laboratory findings from the associated confirmatory analysis (UHPLC-MS, GC-MS, and 1H NMR) to assess the performance of the on-site hand-held Raman spectrometer and outline the challenges of providing real-time analysis of psychoactive substances in a clinical setting. Whilst acknowledging the limitation of the small sample size (n = 13), we demonstrate the potential suitability of using this technology for the purposes of screening substances in community-treatment services. Portability of equipment and timeliness of results are important and only very small samples may be provided by people who use the service. The challenges of accurately identifying substances from complex mixtures were equally found with both point-of-care Raman spectroscopy and laboratory confirmatory-analysis techniques. Further studies are required to confirm these findings.

In silico studies on recreational drugs: 3D quantitative structure activity relationship prediction of classified and de novo designer benzodiazepines.

Currently, increasing availability and popularity of designer benzodiazepines (DBZDs) constitutes a primary threat to public health. To assess this threat, the biological activity/potency of DBZDs was investigated using in silico studies. Specific Quantitative Structure Activity Relationship (QSAR) models were developed in Forge™ for the prediction of biological activity (IC50 ) on the γ-aminobutyric acid A receptor (GABA-AR) of previously identified classified and unclassified DBDZs. A set of new potential ligands resulting from scaffold hopping studies conducted with MOE® was also evaluated. Two generated QSAR models (i.e. 3D-field QSAR and RVM) returned very good performance statistics (r2  = 0.98 [both] and q2  = 0.75 and 0.72, respectively). The DBZDs predicted to be the most active were flubrotizolam, clonazolam, pynazolam and flucotizolam, consistently with what reported in literature and/or drug discussion fora. The scaffold hopping studies strongly suggest that replacement of the pendant phenyl moiety with a five-membered ring could increase biological activity and highlight the existence of a still unexplored chemical space for DBZDs. QSAR could be of use as a preliminary risk assessment model for (newly) identified DBZDs, as well as scaffold hopping for the creation of computational libraries that could be used by regulatory bodies as support tools for scheduling procedures.

Knowledge and Use of Over-the-counter Drugs in Italy: An Exploratory Survey-based Study in the General Population.

BACKGROUND: During the past decade, the misuse of over-the-counter (OTC) medicines has become a global public health concern, especially among young people. In this study, we aimed to explore the OTC consumption and related misuse in Italy and identify the demographic characteristics of people/individuals involved in this phenomenon, understanding eventual risk factors. METHODS: The study consisted of an anonymous online survey distributed by direct contact and via the Internet between June-November 2021 to the general population living in Italy. Descriptive statistics were reported, and binary regression analyses were performed to identify risk factors for lifetime misuse of OTC. The University of Hertfordshire approved the study (aLMS/SF/UH/02951). RESULTS: The final sample size was composed of 717 respondents. The sample was mainly represented by female (69.3%) students (39.9%) in the 20-25 years age group (30.0%). Based on the survey responses, study participants were divided into two groups according to the presence/absence of OTC abuse/misuse (127 versus 590), which were compared for possible predictors of OTC diversion. Multivariate regression showed that OTC abuse/misuse was associated with the knowledge of the effects of OTC [odds ratio/OR = 2.711, 95%Confidence Interval/CI 1.794-4.097, p <0.001]. On the contrary, the educational level appeared to be a protective factor [OR = 0.695, 95%CI 0.58-0.94, p = 0.016]. CONCLUSION: Although, according to our data, the phenomenon of OTC abuse appeared to be limited, increasing attention is needed because of possible underestimation and high-risk outcomes. Preventive strategies, including simplified access to information, may play a key role in limiting OTC misuse.

Alprazolam-related deaths in Scotland, 2004-2020.

BACKGROUND: The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and consumption have increased. Concern about increasing numbers of alprazolam-related fatalities started circulating in 2018. However, statistics on this issue are very limited. This study examined patterns in such mortality in Scotland. METHODS: Statistics on deaths where alprazolam was mentioned in the 'cause of death' were obtained from official mortality registers. Anonymised Scottish case-level data were obtained. Data were examined in respect of the characteristics of decedents and deaths using descriptive statistics. RESULTS: Scotland registered 370 deaths in 2004-2020; 366 of these occurred in 2015-2020: most involved males (77.1%); mean age 39.0 (SD 12.6) years. The principal underlying cause of death was accidental poisoning: opiates/opioids (77.9%); sedatives/hypnotics (15.0%). Two deaths involved alprazolam alone. Main drug groups implicated: opiates/opioids (94.8%), 'other benzodiazepines' (67.2%), gabapentinoids (42.9%), stimulants (30.1%), antidepressants (15.0%). Two-thirds (64.2%) involved combinations of central nervous system (CNS) depressants. DISCUSSION: Alprazolam-related deaths are likely due to an increasing illicit supply. The fall in deaths in 2019-2020 is partially due to increased use of designer benzodiazepines. Treatment for alprazolam dependence is growing. Clinicians need to be aware of continuing recreational alprazolam use. When such consumption occurs with CNS depressants, overdose and death risks increase. CONCLUSIONS: More awareness of alprazolam contributing to deaths, especially in conjunction with other CNS depressants, is needed by consumers and clinicians. Improved monitoring of illicit supplies could identify emerging issues of medicines' abuse.

Pharmacovigilance Signals of the Opioid Epidemic over 10 Years: Data Mining Methods in the Analysis of Pharmacovigilance Datasets Collecting Adverse Drug Reactions (ADRs) Reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS).

In the past twenty years, the consumption of opioid medications has reached significant proportions, leading to a rise in drug misuse and abuse and increased opioid dependence and related fatalities. Thus, the purpose of this study was to determine whether there are pharmacovigilance signals of abuse, misuse, and dependence and their nature for the following prescription opioids: codeine, dihydrocodeine, fentanyl, oxycodone, pentazocine, and tramadol. Both the pharmacovigilance datasets EudraVigilance (EV) and the FDA Adverse Events Reporting System (FAERS) were analyzed to identify and describe possible misuse-/abuse-/dependence-related issues. A descriptive analysis of the selected Adverse Drug Reactions (ADRs) was performed, and pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean) were computed for preferred terms (PTs) of abuse, misuse, dependence, and withdrawal, as well as PTs eventually related to them (e.g., aggression). From 2003 to 2018, there was an increase in ADR reports for the selected opioids in both datasets. Overall, 16,506 and 130,293 individual ADRs for the selected opioids were submitted to EV and FAERS, respectively. Compared with other opioids, abuse concerns were mostly recorded in relation to fentanyl and oxycodone, while tramadol and oxycodone were more strongly associated with drug dependence and withdrawal. Benzodiazepines, antidepressants, other opioids, antihistamines, recreational drugs (e.g., cocaine and alcohol), and several new psychoactive substances, including mitragynine and cathinones, were the most commonly reported concomitant drugs. ADRs reports in pharmacovigilance databases confirmed the availability of data on the abuse and dependence of prescription opioids and should be considered a resource for monitoring and preventing such issues. Psychiatrists and clinicians prescribing opioids should be aware of their misuse and dependence liability and effects that may accompany their use, especially together with concomitant drugs.

A Focus on Abuse/Misuse and Withdrawal Issues with Selective Serotonin Reuptake Inhibitors (SSRIs): Analysis of Both the European EMA and the US FAERS Pharmacovigilance Databases.

Despite increasing reports, antidepressant (AD) misuse and dependence remain underestimated issues, possibly due to limited epidemiological and pharmacovigilance evidence. Thus, here we aimed to determine available pharmacovigilance misuse/abuse/dependence/withdrawal signals relating to the Selective Serotonin Reuptake Inhibitors (SSRI) citalopram, escitalopram, paroxetine, fluoxetine, and sertraline. Both EudraVigilance (EV) and Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) datasets were analysed to identify AD misuse/abuse/dependence/withdrawal issues. A descriptive analysis was performed; moreover, pharmacovigilance measures, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM) were calculated. Both datasets showed increasing trends of yearly reporting and similar signals regarding abuse and dependence. From the EV, a total of 5335 individual ADR reports were analysed, of which 30% corresponded to paroxetine (n = 1592), 27% citalopram (n = 1419), 22% sertraline (n = 1149), 14% fluoxetine (n = 771), and 8% escitalopram (n = 404). From FAERS, a total of 144,395 individual ADR reports were analysed, of which 27% were related to paroxetine, 27% sertraline, 18% citalopram, 16% fluoxetine, and 13% escitalopram. Comparing SSRIs, the EV misuse/abuse-related ADRs were mostly recorded for citalopram, fluoxetine, and sertraline; conversely, dependence was mostly associated with paroxetine, and withdrawal to escitalopram. Similarly, in the FAERS dataset, dependence/withdrawal-related signals were more frequently reported for paroxetine. Although SSRIs are considered non-addictive pharmacological agents, a range of proper withdrawal symptoms can occur well after discontinuation, especially with paroxetine. Prescribers should be aware of the potential for dependence and withdrawal associated with SSRIs.

Designer Benzodiazepines' Activity on Opioid Receptors: A Docking Study.

BACKGROUND: Previous studies have reported that benzodiazepines (BZDs) seem to enhance euphoric and reinforcing properties of opioids in opioid users so that a direct effect on opioid receptors has been postulated, together with a possible synergistic induction of severe side effects due to co use of BDZs and opioids. This is particularly worrisome given the appearance on the market of designer benzodiazepines (DBZDs), whose activity/toxicity profiles are scarcely known. OBJECTIVES: This study aimed to evaluate, through computational studies, the binding affinity (or lack thereof) of 101 DBZDs identified online on the kappa, mu, and delta opioid receptors (K, M, DOR); and to assess whether their mechanism of action could include activation of the latter. METHODS: MOE® was used for the computational studies. Pharmacophore mapping based on strong opioids agonist binders' 3D chemical features was used to filter the DBZDs. Resultant DBZDs were docked into the crystallised 3D active conformation of KOR (PDB6B73), DOR (PDB6PT3) and MOR (PDB5C1M). Co-crystallised ligands and four strong agonists were used as reference compounds. A score (S, Kcal/mol) representative of the predicted binding affinity, and a description of ligand interactions were obtained from MOE®. RESULTS: The docking results, filtered for S < -8.0 and the interaction with the Asp residue, identified five DBZDs as putative binders of the three ORs : ciclotizolam, fluloprazolam, JQ1, Ro 48-6791, and Ro 48-8684. CONCLUSION: It may be inferred that at least some DBZDs may have the potential to activate opioid receptors. This could mediate/increase their anxiolytic, analgesic, and addiction potentials, as well as worsen the side effects associated with opioid co-use.

Benefits and Harms of 'Smart Drugs' (Nootropics) in Healthy Individuals.

'Smart drugs' (also known as 'nootropics' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory, attention, learning, executive functions and vigilance, hence the reference to a 'pharmaceutical cognitive doping behaviour'. While the efficacy of known CEs in individuals with memory or learning deficits is well known, their effect on non-impaired brains is still to be fully assessed. This paper aims to provide an overview on the prevalence of use; putative neuroenhancement benefits and possible harms relating to the intake of the most popular CEs (e.g. amphetamine-type stimulants, methylphenidate, donepezil, selegiline, modafinil, piracetam, benzodiazepine inverse agonists, and unifiram analogues) in healthy individuals. CEs are generally perceived by the users as effective, with related enthusiastic anecdotal reports; however, their efficacy in healthy individuals is uncertain and any reported improvement temporary. Conversely, since most CEs are stimulants, the related modulation of central noradrenaline, glutamate, and dopamine levels may lead to cardiovascular, neurological and psychopathological complications. Furthermore, use of CEs can be associated with paradoxical short- and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. Finally, the non-medical use of any potent psychotropic raises serious ethical and legal issues, with nootropics having the potential to become a major public health concern. Further studies investigating CE-associated social, psychological, and biological outcomes are urgently needed to allow firm conclusions to be drawn on the appropriateness of CE use in healthy individuals.

NPS detection in prison: A systematic literature review of use, drug form, and analytical approaches.

This paper presents a systematic literature review on the detection of new psychoactive substances (NPS) in prison settings. It includes the most frequently reported NPS classes, the routes and forms used for smuggling, and the methods employed to analyse biological and non-biological samples. The search was carried out using MEDLINE (EBSCO), Scopus (ELSEVIER), PubMed (NCBI), and Web of Science (Clarivate) databases, along with reports from the grey literature in line with the PRISMA-S guidelines. A total of 2708 records were identified, of which 50 met the inclusion criteria. Findings showed the most prevalent NPS class reported in prison was synthetic cannabinoids (SCs). The most frequently reported SCs in non-biological samples were 4F-MDMB-BINACA, MDMB-4en-PINACA, and 5F-ADB. These were smuggled mainly through the postal services deposited on paper or herbal matrices. Concentrations of SCs detected on seized paper ranged between 0.05 and 1.17 mg/cm2 . The SCs most frequently reported in biological specimens (i.e., urine, blood, saliva, and wastewater) were 5F-MDMB-PICA, 4F-MDMB-BINACA, and MDMB-4en-PINACA. Concentrations of SCs reported in femoral blood and serum were 0.12-0.48 ng/ml and 34-17 ng/ml, respectively. Hyphenated techniques were predominantly employed and generally successful for the detection of NPS in biological (i.e., LC-HRMS/MS) and non-biological samples (i.e., LC-HRMS/MS and GC-MS). The onsite technique IMS showed promise for detecting SCs in various forms; however, immunoassays were not recommended. Future work should focus on accurate in-field detection of SCs deposited on paper and in urine and saliva to improve real-time decision-making, as well as wastewater and air monitoring for overall drug use trends.

Misuse of Anticholinergic Medications: A Systematic Review.

(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP (n = 25), and benztropine (n = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.