Search Results (9)

Background: Recent drug enforcement activities have possibly suggested the presence of some calcium channel blocker antihypertensives in association with cocaine. The seizure revealed the possibility that the two drugs might have been used together for some unknown reasons. Methods: Hence, this study aimed at investigating the nature and frequency of adverse drug reactions (ADRs) reported in association with the concomitant use of calcium channel blockers (CCBs) and cocaine, using data from the FDA Adverse Event Reporting System (FAERS). Results: After removing duplicate reports, a total of 67 cases involving concomitant use of cocaine and CCBs were analyzed and were stratified into three groups based on the CCB involved: verapamil (n = 19), diltiazem (n = 30), and amlodipine (n = 18). Logistic regression analysis identified “product use for unknown indication” (β = 0.33) as the strongest predictor of fatal outcomes. Age revealed a modest negative association with fatal outcome (β = −0.93, intercept = 4.07). Concomitant substance use was reported in over 84% of cases. Frequently co-used substances included opioids, benzodiazepines, antidepressants, antihistamines, and alcohol. Poly-drug use was most pronounced in the diltiazem group, which exhibited the highest burden of opioid and alcohol co-exposure. Conclusions: It is here suggested that clinicians should exercise caution when managing individuals who use cocaine, due to the potential for increased toxicity and lethality when CCBs are co-used, either as part of a prescribed treatment or if CCBs are present as adulterants in cocaine. Full article

Background: “Chemsex” involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, “poppers”, type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This paper aims to provide an overview of the clinical pharmacology of the vast range of drugs that are being used for chemsex with a focus on both the medical and psychopathological disturbances that they can produce. Methods: A narrative literature review was conducted using Pubmed, Scopus, and Web of Science databases. A total of 273 papers published up to January 2025 were screened; articles were selected based on relevance to chemsex/sexualized used behaviour and related substances. Both human and preclinical studies were considered. Results: The use of stimulants is likely related to the need to increase as much as possible both sexual arousal and performance but also to increase social interactions. Furthermore, the empathogenic/entactogenic activities of some MDMA-like “love drugs” facilitate the occurrence of “feeling closer/more intimate” emotional sensations, and GHB/GBL may provide the user with a subjective sensation of disinhibition, hence facilitating condomless meetings with a higher number of random partners. Conversely, ketamine may be used to both enjoy its psychotropic dissociative characteristics and facilitate the potentially painful receptive anal intercourse and/or fisting experiences. Most typically, these drugs are consumed in combination, with polydrug exposure possibly facilitating the occurrence of serotonergic syndrome, seizures, drug–drug pharmacokinetics’ interaction, and sympathomimetic overstimulation. Following these polydrug exposures, a range of psychopathological conditions have at times been reported. These issues may lead to misuse of opiates/opioids, gabapentinoids, and/or antipsychotics. Conclusions: Further actions should aim at reducing the stigma that prevents individuals from accessing necessary healthcare and support services. A multidisciplinary approach that combines medical, psychological, and social support remains key to managing the complex challenges posed by chemsex-related drug use. Full article

Background/Objectives: The misuse of veterinary drugs is a growing concern, with increasing evidence of their presence in illicit drug markets and their use as alternatives to traditional substances. Methods: This study explores Reddit discussions on the misuse of veterinary drugs on Reddit, focusing on xylazine, carfentanil, medetomidine, pentobarbital, phenylbutazone, and acepromazine. Reddit was utilised for its abundant real-time data on users’ thoughts and experiences with substance misuse. Through a combination of manual and Artificial Intelligence (AI)-driven thematic analysis, we examined posts and comments to explore patterns of misuse. Results: The themes analysed included adverse effects, polysubstance misuse, routes of administration, motivations for misuse, and methods of obtaining these drugs. Our findings revealed that xylazine, medetomidine, carfentanil, and pentobarbital exhibit significant potential for misuse, while phenylbutazone and acepromazine are not widely misused. Despite this, phenylbutazone and acepromazine have been identified as adulterants in the illicit drug supply in the United States. The most discussed themes included motivations for misuse, followed by public experiences and perceptions, as well as adverse effects. Conclusions: The dual-method approach of combining manual interpretation with AI analysis allowed for a comprehensive understanding of social media discussions. This research highlights the importance of monitoring online platforms for early indicators of emerging drug trends, offering valuable insights to inform public health policies and intervention strategies. Impact Statement: This research highlights the growing public health risk posed by veterinary drug misuse, underscoring the need for enhanced monitoring, regulatory frameworks, and education to address their diversion into illicit markets. By leveraging social media as an early detection tool for emerging drug trends, our findings can inform targeted interventions. Full article

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. Full article

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has gained considerable attention as a therapeutic agent for type 2 diabetes mellitus and obesity. Despite its clinical success, the precise mechanisms underlying its pharmacological effects remain incompletely understood. In this study, we employed ligand-based drug design strategies to investigate potential off-target interactions of semaglutide. Through a comprehensive in silico screening of semaglutide’s structural properties against a diverse panel of proteins, we have identified calmodulin (CaM) as a putative novel target of semaglutide. Molecular docking simulations revealed a strong interaction between semaglutide and CaM, characterized by favourable binding energies and a stable binding pose. Further molecular dynamics simulations confirmed the stability of the semaglutide–CaM complex, emphasizing the potential for a physiologically relevant interaction. In conclusion, our ligand-based drug design approach has uncovered calmodulin as a potential novel target of semaglutide. This discovery sheds light on the complex pharmacological profile of semaglutide and offers a promising direction for further research into the development of innovative therapeutic strategies for metabolic disorders. The CaM, and especially so the CaMKII, system is central in the experience of both drug- and natural-related reward. It is here hypothesized that, due to semaglutide binding, the reward pathway-based calmodulin system may be activated, and/or differently regulated. This may result in the positive semaglutide action on appetitive behaviour. Further studies are required to confirm these findings. Full article

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. Full article

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. Full article

Psilocybin has been suggested as a promising transdiagnostic treatment strategy for a wide range of psychiatric disorders. Recent findings showed that psychedelic-assisted/”psycholitic” psychotherapy should provide significant and sustained alleviation of depressive symptoms. However, to date, there have been several study limitations (e.g., small sample sizes, blinding, limited follow-up, highly screened treatment populations) and some health/political issues, including practitioners’ experience, lack of standardized protocols, psychedelics’ legal status, ethical concerns, and potential psychological/psychopathological/medical untoward effects. The focus here is on a range of clinical and methodological issues, also aiming at outlining some possible suggestions. We are confident that newer evidence, more precise protocols, and eventual reclassification policies may allow a better understanding of the real potential of psilocybin as a transdiagnostic therapeutic molecule. Full article

The restrictive measures adopted during the COVID-19 pandemic modified some previously consolidated drug use patterns. A focus on social networks allowed drug users to discuss, share opinions and provide advice during a worldwide emergency context. In order to explore COVID-19-related implications on drug trends/behaviour and on most popular psychotropic substances debated, the focus here was on the constantly updated, very popular, Reddit social platform’s posts and comments. A quantitative and qualitative analysis of r/Drugs and related subreddits, using a social media listening netnographic approach, was carried out. The post/comments analysed covered the time-frame December 2019–May 2020. Between December 2019 and May 2020, the number of whole r/Drugs subreddit members increased from 619,563 to 676,581 members, respectively, thus increasing by 9.2% by the end of the data collection. Both the top-level r/Drugs subreddit and 92 related subreddits were quantitatively analysed, with posts/comments related to 12 drug categories. The drugs most frequently commented on included cannabinoids, psychedelics, opiates/opioids, alcohol, stimulants and prescribed medications. The qualitative analysis was carried out focussing on four subreddits, relating to some 1685 posts and 3263 comments. Four main themes of discussion (e.g., lockdown-associated immunity and drug intake issues; drug-related behaviour/after-quarantine plans’ issues; lockdown-related psychopathological issues; and peer-to-peer advice at the time of COVID-19) and four categories of Redditors (e.g., those continuing the use of drugs despite the pandemic; the “couch epidemiologists”; the conspirationists/pseudo-science influencers; and the recovery-focused users) were tentatively identified here. A mixed-methods, social network-based analysis provided a range of valuable information on Redditors’ drug use/behaviour during the first phase of the COVID-19 pandemic. Further studies should be carried out focusing on other social networks as well as later phases of the pandemic. Full article