Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis.

INTRODUCTION: The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA). AIM: The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators. METHODS: Descriptive and pharmacovigilance disproportionality analyses was performed. RESULTS: A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 'serious' cases related to selected ADRs were registered during 2005-2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide). DISCUSSION: Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations. CONCLUSIONS: With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.

Stimulant and hallucinogenic novel psychoactive substances; an update.

INTRODUCTION: The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these drugs' clinical and pharmacological issues. AREAS COVERED: The focus here was on: stimulants (e.g. amphetamines, methamphetamine, and pseudoephedrine; phenethylamines; synthetic cathinones; benzofurans; piperazines; aminoindanes; aminorex derivatives; phenmetrazine derivatives; phenidates); classical (e.g. ergolines; tryptamines; psychedelic phenethylamines), and atypical (e.g. PCP/ketamine-like dissociatives) psychedelics.Stimulant and psychedelics are associated with: a) increased central DA levels (psychedelic phenethylamines, synthetic cathinones and stimulants); b) 5-HT receptor subtypes' activation (psychedelic phenethylamines; recent tryptamine and lysergamide derivatives); and c) antagonist activity at NMDA receptors, (phencyclidine-like dissociatives). EXPERT OPINION: Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of index novel psychoactives can be organized. The future of psychedelic research should focus on identifying robust study designs to convincingly assess the potential therapeutic benefits of psychedelics, molecules likely to present with limited dependence liability levels.

New/emerging psychoactive substances and associated psychopathological consequences.

BACKGROUND: The present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects. METHODS: NPS have been identified through an innovative crawling/navigating software, called the 'NPS.Finder®', created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available. RESULTS: Using the 'NPS.Finder®' approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines. CONCLUSIONS: The ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.

"Purple Drank" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications.

In the early 1990s, several studies reported the misuse of codeine and promethazine hydrochloride cough syrup. Since then, the combination of this pharmaceutical, together with sprite or alcohol, known on the streets as "purple drank" or "lean", has become a popular drug among rap singers who promote its tranquilizing and euphoric effects through their music and videos. This review examines the "purple drank" phenomenon, taking into consideration its clinical and social implications. The study was conducted using PubMed, Scopus, and Web of Science as search engines, applying several inclusion and exclusion criteria and the string "Purple AND drank", resulting in 138 records. Seven papers that met our criteria were found. The risk of bias assessment, when applicable, was also considered, resulting in a low level of risk. Epidemiological data highlighted a heterogeneous diffusion of the misuse of this mixture, which is not exclusively linked to a specific type of user (African-American teenagers, athletes, and rappers), as previously reported in American newspapers and in the social media. New digital tools should be taken into consideration for further social and medical evaluations of this phenomenon.

New Psychoactive Substances (NPS) - a Challenge for the Addiction Treatment Services.

Over the last few years, hundreds of new psychoactive substances (NPS) have been identified in Europe. Apart from some herbal compounds, NPS mainly include synthetic cannabinoids and a range of new synthetic stimulants (e. g., cathinones). Synthetic NPS are often developed whilst modifying the basic chemical (e. g., phenethylamine or tryptamine) structure. Although the pharmacology and toxicology of most NPS are hardly known, they are being offered, especially online, as "bath salts," as "incense mixtures," or under other misleading labels. In addition, NPS are advertised as "legal highs," suggesting that, in contrast to substances regulated by the national laws, trading with NPS is legal. Although only little is known about the prevalence of NPS use, some of these molecules may be associated with a range of severe adverse reactions. Indeed, different from cannabis, synthetic cannabinoid users may present with epileptic seizures, loss of consciousness, and a range of persisting psychopathological disorders. Future studies should inform better-tailored management strategies.

The "Eyeballing" technique: an emerging and alerting trend of alcohol misuse.

OBJECTIVE: Alternative methods of alcohol consumption have recently emerged among adolescents and young adults, including the alcohol "eyeballing", which consist in the direct pouring of alcoholic substances on the ocular surface epithelium. In a context of drug and behavioural addictions change, "eyeballing" can be seen as one of the latest and potentially highly risky new trends. We aimed to analyze the existing medical literature as well as online material on this emerging trend of alcohol misuse. MATERIALS AND METHODS: Literature on alcohol eyeballing was searched in PsychInfo and Pubmed databases. Results were integrated with a multilingual qualitative assessment of the database provided by The Global Public Health Intelligence Network (GPHIN) and of a range of websites, drug fora and other online resources between March 2013 and July 2013. RESULTS: Alcohol eyeballing is common among adolescents and young adults; substances with high alcohol content, typically vodka, are used for this practice across the EU and internationally. The need for a rapid/intense effect of alcohol, competitiveness, novelty seeking and avoidance of "alcoholic fetor" are the most frequently reported motivations of "eyeballers". Local effects of alcohol eyeballing include pain, burning, blurred vision, conjunctive injection, corneal ulcers or scarring, permanent vision damage and eventually blindness. CONCLUSIONS: Alcohol eyeballing represents a phenomenon with potential permanent adverse consequences, deserving the attention of families and healthcare providers. Health and other professionals should be informed about this alerting trend of misuse. Larger observational studies are warranted to estimate the prevalence, characterize the effects, and identify adequate forms of interventions for this emerging phenomenon.

Effects of ketamine on psychomotor, sensory and cognitive functions relevant for driving ability.

Ketamine is a dissociative anesthetic. The misuse of ketamine as a recreational drug has increased over the last decade, especially in rave parties or clubs. Short-term ketamine pilot protocols have been undertaken for treatment-resistant depressive clients. In this study, we review and comment on the evidence relating to the potential of ketamine as a causative/contributory factor in traffic accidents. To determine the causal role of ketamine in traffic accidents, a literature search on the psychomotor, cognitive, visual and perceptual functions related to safe driving was conducted. Furthermore, to interpret related data better, an overview of ketamine and its congeners' clinical pharmacology issues, recreational psychoactive effects, and identification in biological specimens is also provided.

Impact of community pharmacy diabetes monitoring and education programme on diabetes management: a randomized controlled study.

AIMS: To evaluate the impact of a pharmacist-led patient education and diabetes monitoring programme on HbA(1c) and other cardiovascular risk factors in the community setting. METHODS: Patients with Type 2 diabetes (n = 46) attending two community pharmacies in Hertfordshire, UK were randomized to one of two groups. Patients in the intervention group (n = 23) received a programme of education about diabetes, its treatment and associated cardiovascular risk factors. These patients were seen for monitoring/counselling by a community pharmacist on six occasions over a 12-month period. Measures included HbA(1c), BMI, blood pressure, blood glucose and lipid profile. Patients in the control group (n = 23) underwent these measurements at baseline and at 12 months only, without specific counselling or education over and above usual care. RESULTS: HbA(1c) fell from 66 mmol/mol (8.2%) to 49 mmol/mol (6.6%) (P < 0.001) in intervention group, compared with reduction from 65 mmol/mol (8.1%) to 59 mmol/mol (7.5%) in the control group (P = 0.03). Blood pressure fell from 146/87 to 126/81 mmHg in the intervention group (P = 0.01) compared with no significant change in the control group (136/86 to 139/82 mmHg). Significant reductions in BMI (30.8 to 27 kg/m(2), P < 0.001) and blood glucose (8.8 to 6.9 mmol/l, P < 0.001) were also observed in the intervention group as compared with no significant changes in the control group. Lipid profile changes were mixed. In the intervention group, improvements were seen in diabetes-related quality of life (P = 0.001), diabetes knowledge (P = 0.018), belief about the need for medication (P = 0.004) and reduced concerns regarding medication (P < 0.001). CONCLUSIONS: Education and counselling by community pharmacists can result in favourable improvements to the cardiovascular risk profile of patients with Type 2 diabetes.

Differences in drug consumption, comorbidity and health service use of opioid addicts across six European urban regions (TREAT-project).

OBJECTIVES: This comparative study investigated consumption patterns, comorbidity and treatment utilization of opioid addicts in six European cities (Athens, Essen, London, Padua, Stockholm, Zurich). SUBJECTS AND METHODS: Data were collected by structured face-to-face interviews. The representative sample comprises 599 addicts (100 patients per centre, 99 in London) at the start of a treatment episode. RESULTS: Patients were dependent on opioids for about 10 years. Regional differences were significant regarding the patients' drug consumption pattern and their method of heroin administration (up to a fourth of the patients in Essen, London and Zurich usually smoke heroin). Concomitant use of benzodiazepines, cannabis and alcohol was common in all regions with the German and English samples showing the highest level of polydrug use. The prevalence of major depression was high in all regions (50%). Stockholm and London patients worry most about their physical health. Differences in the amount of needle sharing and especially in the use of public health service were prominent between the sites. Opioid addiction was a long-term disorder associated with a high burden of comorbidity and social problems in all cities. CONCLUSION: The results of the study show significant interregional differences of opioid addicts which might require different treatment strategies in European countries to handle the problem.

Numerical simulations of Rayleigh-Taylor front evolution in turbulent stratified fluids.

We present state-of-the-art numerical simulations of a two-dimensional Rayleigh-Taylor instability for a compressible stratified fluid. We describe the computational algorithm and its implementation on the QPACE supercomputer. High resolution enables the statistical properties of the evolving interface that we characterize in terms of its fractal dimension to be studied.

The Gamblers' Temperament and Character Inventory (TCI) personality profile.

In a cross-comparison study, the Cloninger's Temperament and Character Inventory (TCI) personality profile was administered to 28 probable pathological gamblers (PPGs), 32 nonpathological gamblers (non-PGs), and 65 controls. As a screening device, the validated Italian version of the South Oak Gambling Screen was administered to all subjects. Novelty Seeking (NS) values were higher in PPGs in comparison with both non-PGs (p < .05) and controls (p < .001). PPGs showed lower Self-Directedness (SD) and Cooperativeness (CO) values with respect to both non-PGs (p < .05 and p = .001, respectively) and controls (p < .001 and p = .001, respectively). The subsamples of PPGs reporting either a current substance misuse condition or a parental involvement in gambling/substance misuse showed higher NS (p = .01) and lower CO (p = .005) values than the remaining PPGs. A duration of problem gambling in excess of 20 years was associated with lower (p = .001) CO values. Specific temperamental (NS) and character (SD; CO) dimensions differentiated PPGs from both non-PGs and controls; assessment of personality profile with the TCI may identify at-risk social gamblers.

Review of deaths related to analgesic- and cough suppressant-opioids; England and Wales 1996-2002.

OBJECTIVE: The data on England and Wales voluntarily supplied by Coroners to the National Programme on Substance Abuse Deaths for the August 1996-December 2002 time frame were analyzed. METHODS: All cases in which at least one analgesic- and cough suppressant-opioid other than heroin/morphine, methadone or buprenorphine was identified were extracted from the database. We hypothesized that: a) populations of addicts and non-addicts presented differences in patterns of drugs involved; and b) within the population of addicts and non-addicts, intentional and non-intentional deaths presented different patterns of substance consumption. RESULTS: A total of 2024 deaths related to selected opioids, either alone or in combination, were included in the analysis. Typically, non-addicts were older than 45 and died as a result of intentional poisoning whilst majority of addicts were young, males and victims of accidental deaths. In about 93% of cases the selected opioids were reported in combination with another substance. Most frequently identified narcotics were propoxyphene, codeine and dihydrocodeine. Co-proxamol, Co-codamol and Co-dydramol were typically prescribed for non-addicts, whilst dihydrocodeine was mostly given to addicts. In non-addicts, alcohol was mostly represented in accidental deaths and antidepressants were typically represented in intentional deaths. Conversely, illicit drugs and hypnotics/sedatives were typically reported in addicts' accidental deaths. CONCLUSIONS: The present report constitutes the largest available collection of analgesic- and cough suppressant-opioid mortality data in the UK. Users should be educated about risks associated with polydrug misuse.

[Salvia divinorum--representation of a new drug in the Internet]. / Salvia divinorum--Präsenz einer neuen Droge im Internet.

AIM OF THE STUDY: The German pages of the Internet were searched for the presence of the hallucinogenic herbal drug Salvia divinorum, which is not dealt with in current addiction medicine or psychiatric text books. The investigation is part of the EU sponsored project "Psychonaut" as preparatory work for the development of an Internet-based early warning system. METHODS: The first 100 websites of the search using "Salvia divinorum" were compared with the search results for "cannabis" and "LSD". The following aspects of the sites were especially analyzed: the originator, marketing of drugs, and the attitude towards drug use. RESULTS: Salvia was offered for sale on approximately a third of the sites (29%); cannabis and LSD were not marketed on any sites. Official websites such as those from governmental organizations or universities were seldom found when searching for "Salvia divinorum", and then only under the last hits. The percentage of institutional sites (e. g. public organizations) were 12% with Salvia, 21% with cannabis, and 38% with LSD. A drug-friendly attitude was found at 64 % of the sites with regard to Salvia, 58% for cannabis, and 24% for LSD. CONCLUSION: The drug help system must be aware of that the Internet is a source of drug-related information, and of drug trade. As this investigation shows, sites often have a drug-friendly attitude. The low availability of official information on Salvia divinorum (also outside the Internet) relative to the presence of drug-friendly or drug trading sites is an indication that new trends of drug consumption can be tracked in the Internet before they will be found in official literature.

Pattern of cannabis use in ecstasy polydrug users: moderate cannabis use may compensate for self-rated aggression and somatic symptoms.

Cannabis is one of the most common 'co-drugs' for ecstasy users. The aim of the present study was to explore self-reported psychobiological problems in ecstasy polydrug users in relation to their pattern of cannabis use. Two hundred and eighty ecstasy polydrug users were allocated into five cannabis groups according to the frequency of their cannabis use. The control group comprised 121 alcohol-tobacco users. There were no significant group differences with regard to age, diagnosed family psychiatric history and level of self-rated stress experienced during 6 months prior to the study. The present study produced three main findings: (a) Ecstasy users with no concomitant use of cannabis displayed more self-rated aggression and somatic symptoms compared with ecstasy users who were smoking cannabis on a monthly or weekly basis. (b) Ecstasy users who reported heavy cannabis use in the past displayed higher paranoid symptoms compared with ecstasy weekly and daily cannabis users. (c) Former heavy cannabis users were the most likely to complain of a variety of ecstasy related long-term problems. In conclusion, moderate cannabis use may help to ameliorate or mask MDMA-induced aggressivity and somatic symptoms. However, this study confirms that heavy cannabis and ecstasy use is associated with several psychobiological problems, which may emerge after a period of abstinence from both drugs.