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.

Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature.

BACKGROUND: Ibogaine and noribogaine are psychedelic substances with dissociative properties naturally occurring in plants of the Apocynaceae family. Research has shown their efficacy in treating substance use disorders (SUD), particularly in opiate detoxification, but their efficacy and toxicity are still unclear. OBJECTIVE: This review aims to assess the anti-addictive role of ibogaine and evaluate its side effects. METHODS: A systematic literature review was conducted on the 29th of November 2021 using PubMed, Scopus and Web of Science databases through the following search strategy: ("Ibogaine" OR "Noribogaine") AND ("SUD" OR "substance use disorder" OR "craving" OR "abstinence" OR "withdrawal" OR "addiction" OR "detoxification") NOT animal NOT review NOT "vitro." The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed for data gathering purposes. Research methods were registered on PROSPERO (CRD42021287034). RESULTS: Thirty-one articles were selected for the systematic revision, and two were considered for analysis. The results were organised according to the type of study: case reports/case series, randomised- controlled trials (RCTs), open-label, survey and observational studies. The main outcomes were related to the anti-addictive effect of ibogaine and its cardiac toxicity. A meta-analysis of side effects was conducted using RevMan 5.4 software, showing a significant risk of developing headaches after ibogaine/noribogaine treatment. CONCLUSION: The results show some efficacy of ibogaine in the treatment of SUDs, but its cardiotoxicity and mortality are worrying. Further studies are needed to assess its therapeutic efficacy and actual safety.

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.

Hearing impairment in children living with HIV in Haiti.

OBJECTIVE: To identify the prevalence of hearing impairment and associated risk factors in children living with human immunodeficiency virus (HIV) in Haiti. METHODS: A validated smartphone-based platform with pure-tone audiometry was used to screen 341 HIV-infected children for hearing impairment in Port-au-Prince, Haiti from March 2019 to September 2020. If screening was failed, a more comprehensive pure-tone audiometric evaluation was administered. Demographic, otologic, and HIV-related data were obtained through caregiver surveys and medical charts. Statistical analysis included univariate and multivariate logistic regression. RESULTS: Sixty (18%) of 341 HIV-infected children (ages 7-18 years) had hearing impairment. Of those failing their hearing assessment, 17 (28%) had moderate and 5 (8%) had severe or profound hearing loss. Hearing impairment was associated with frequent ear infections (OR 3.37; 95% CI 1.76-6.46; p < 0.001) and family history of hearing loss (OR 5.12; 95% CI 2.14-12.23; p = 0.001) but not viral load (OR 1.00; 95% CI 0.73-1.02; p = 0.28) or antiretroviral therapy duration (OR 0.96; 95% CI 0.79-1.17; p = 0.66). Only 35% of caregivers correctly perceived their child's hearing loss. CONCLUSIONS: Hearing impairment occurs at a higher prevalence in HIV-infected children in Haiti than what is expected for those living without HIV. Frequent ear infections were significantly associated with hearing loss while antiretroviral therapy duration was not. Despite their potential ototoxicity, antiretroviral therapies should be continued and may decrease incidence of otitis media. Low caregiver perception of hearing loss emphasizes the need for routine hearing screening for HIV-infected children.

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.

Focus on Over-the-Counter Drugs' Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants.

Background: Over the past 20 years or so, the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as ingested for recreational purposes. OTC drugs such as antihistamines, cough/cold medications, and decongestants are reportedly the most popular in being diverted and misused. Objective: While the current related knowledge is limited, the aim here was to examine the published clinical data on OTC misuse, focusing on antihistamines (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate), dextromethorphan (DXM)- and codeine-based cough medicines, and the nasal decongestant pseudoephedrine. Methods: A systematic literature review was carried out with the help of Scopus, Web of Science databases, and the related gray literature. For data gathering purposes, both the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and PROSPERO guidelines were followed (PROSPERO identification code CRD42020209261). Results: After completion of the selection, eligibility, and screening phases, some 92 articles were here taken into consideration; case reports, surveys, and retrospective case series analyses were included. Findings were organized according to the specific OTC recorded. Most articles focused here on DXM (n = 54) and diphenhydramine (n = 12). When specified, dosages, route(s) of administration, toxicity symptoms (including both physical and psychiatric ones), and outcomes were here reported. Conclusion: Results from the systematic review showed that the OTC misusing issues are both widespread worldwide and popular; vulnerable categories include adolescents and young adults, although real prevalence figures remain unknown, due to a lack of appropriate monitoring systems. Considering the potential, and at times serious, adverse effects associated with OTC misusing issues, healthcare professionals should be vigilant, and ad hoc preventative actions should be designed and implemented.

Case Report: Treatment of Kratom Use Disorder With a Classical Tricyclic Antidepressant.

Kratom or Mitragyna speciosa (Korth.) is an evergreen tree of the coffee family native to South-East Asia and Australasia. It is used by locals recreationally to induce stimulant and sedative effects and medically to soothe pain and opiate withdrawal. Its leaves are smoked, chewed, or infused, or ground to yield powders or extracts for use as liquids. It contains more than 40 alkaloids; among these, mitragynine and 7-hydroxymitragynine are endowed with variable mu, delta, and kappa opioid stimulating properties (with 7-hydroxymitragynine having a more balanced affinity), rhynchophylline, which is a non-competitive NMDA glutamate receptor antagonist, but is present in negligible quantities, and raubasine, which inhibits α1-adrenceptors preferentially over α2-adrenceptors, while the latter are bound by 7-hydroxymitragynine, while mitragynine counters 5-HT2A receptors. This complexity of neurochemical mechanisms may account for kratom's sedative-analgesic and stimulant effects. It is commonly held that kratom at low doses is stimulant and at higher doses sedative, but no cut-off has been possible to define. Long-term use of kratom may produce physical and psychological effects that are very similar to its withdrawal syndrome, that is, anxiety, irritability, mood, eating, and sleep disorders, other than physical symptoms resembling opiate withdrawal. Kratom's regulatory status varies across countries; in Italy, both mitragynine and the entire tree and its parts are included among regulated substances. We describe the case of a patient who developed anxiety and dysphoric mood and insomnia while using kratom, with these symptoms persisting after withdrawal. He did not respond to a variety of antidepressant combinations and tramadol for various months, and responded after 1 month of clomipramine. Well-being persisted after discontinuing tramadol.

The e-psychonaut drugs' psychopharmacology.

The focus here was on the pharmacological and clinical pharmacological issues pertaining to the vast range of drugs (e.g. synthetic cannabimimetics, synthetic opioids, novel stimulants, novel psychedelics, PCP/ketamine-like compounds, prescribed medicinal compounds and popular psychotropic herbs/plants) discussed by Internet-based enthusiasts of new/novel psychoactive substances (NPS), 'e-psychonauts'. Currently ongoing related in silico studies, followed by further in vitro and in vivo/preclinical studies, will hopefully provide important findings in terms of which molecules within each given NPS class may present with higher levels of receptor affinities, and hence clinical potency. Understanding the pharmacological characteristics/potency of those novel recreational molecules will hopefully help in predicting related NPS diffusion, morbidity and possible lethality data.

The e-Psychonauts' 'Spiced' World; Assessment of the Synthetic Cannabinoids' Information Available Online.

BACKGROUND: A wide range of novel psychoactive substances (NPS) is regularly searched and discussed online by web-based drug enthusiasts (i.e. the e-psychonauts). Among NPS, the range of synthetic cannabinoids (SC; 'Spice') currently represents a challenge for governments and clinicians. METHODS: Using a web crawler (i.e. the NPS.Finder®), the present study aimed at assessing psychonauts' fora/platforms to better understand the online mentions of SC. RESULTS: The open-web crawling/navigating software identified here some 1,103 synthetic cannabinoids. Of these, 863 molecules were not listed in either the international or the European NPS databases. CONCLUSION: A web crawling approach helped here in identifying a large range of unknown SC likely to possess a misuse potential. Most of these novel/emerging molecules are still relatively unknown. This is a reason for concern; each of these analogues potentially presents different toxicodynamic profiles and there is a lack of docking, preclinical, and clinical observations. Strengthening multidisciplinary collaboration between clinicians and bioinformatics may prove useful in better assessing SC-associated public health risks.

'New/Designer Benzodiazepines': An Analysis of the Literature and Psychonauts' Trip Reports.

BACKGROUND: NPS belonging to the benzodiazepine (BZD) class, e.g., 'legal/designer BZDs'/'research chemicals', have recently emerged in the drug (mainly online/virtual) market. OBJECTIVE: While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians'/public health knowledge/awareness, to incentive harm reduction strategies. METHOD: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the 'new BZDs' so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts' online trip reports. RESULTS: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. CONCLUSION: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

Impact of the UK Psychoactive Substances Act on awareness, use, experiences and knowledge of potential associated health risks of novel psychoactive substances.

AIMS: The risk of potential harms prompted the UK government to introduce the Psychoactive Substances Act in 2016. The aim of the present study was to evaluate the impact and effectiveness of this new legislation on patterns of novel psychoactive substance (NPS) awareness, use, experiences and risk awareness in a self-selected sample of UK consumers to inform education and policy. METHODS: The Bristol Online Survey was advertised on the Bluelight drug forum and social media Facebook pages and University email between 7 January and 7 February 2015 (168 responses) and 9 March to 18 September 2017 (726 responses). UK country of residence responses were extracted for analysis (SPSS). RESULTS: In a predominantly university-educated, young (< 25 years) self-selecting sample, 1 year after introduction of the legislation, NPS use (in males, under 18s, those educated to school/college level, P < .001) has increased, whilst health risk awareness has not changed and remains poor. Users are switching to sourcing NPSs via street dealers (49%) and the darknet (31%) and showing an increase in preference for the herbal NPS Salvia divinorum (P < .05). The main reasons for NPS use remain the influence of friends (69%) in a social setting and to get high (76%) usually in combination with alcohol, cannabis or ecstasy. CONCLUSION: Regulation alone, so far, has not impacted on health risk awareness, NPS drug demand and culture in our UK survey sample. Alongside regulation, NPS health promotion education (particularly in schools, colleges) is needed that addresses resilience and both the risks and beneficial effects of NPS.

The Bridge Between Classical and "Synthetic"/Chemical Psychoses: Towards a Clinical, Psychopathological, and Therapeutic Perspective.

The critical spread and dissemination of novel psychoactive substances (NPS), particularly among the most vulnerable youngsters, may pose a further concern about the psychotic trajectories related to the intake of new synthetic drugs. The psychopathological pattern of the "new psychoses" appears to be extremely different from the classical presentation. Therefore, clinicians need more data on these new synthetic psychoses and recommendations on how to manage them. The present mini-review aims at deepening both the clinical, psychopathological features of synthetic/chemical NPS-induced psychoses and their therapeutic strategies, according to the different NPS classes implicated, by underlining the main differences with the "classical" psychoses. A comprehensive review was conducted using the PubMed/Medline database by combining the search strategy of free-text terms and exploding a range of MESH headings relating to the topics of novel psychoactive substances and synthetic/chemical psychoses as follows: {(Novel Psychoactive Substances[Title/Abstract]) AND Psychosis[Title/Abstract])} and for each NPS categories as well, focusing on synthetic cannabinoids and cathinones, without time and/or language restrictions. Finally, an overview of the main clinical and psychopathological features between classical versus NPS-induced chemical/synthetic psychoses is provided for clinicians working with dual disorders and addiction psychiatry. Further insight is given here on therapeutic strategies and practical guidelines for managing patients affected with synthetic/chemical NPS-induced psychoses.

The use of new psychoactive substances (NPS) in young people and their role in mental health care: a systematic review.

Introduction: Over the past 10 years, a large number of New Psychoactive Substances (NPS) have entered the recreational drug scenario. NPS intake has been associated with health-related risks, and especially so for vulnerable populations such as the youngsters. Currently, most knowledge on the NPS health effects is learnt from both a range of users' reports, made available through the psychonauts' web fora, and from the few published, related toxicity, clinical observations.Areas covered: This paper aims at providing an overview of NPS effects on youngsters' mental health, whilst performing a systematic review of the current related knowledge.Expert opinion: NPS consumption poses serious health risks, due to both a range of unpredictable clinical pharmacological properties and the typical concomitant use of other psychoactive molecules; overall, this can lead to near misses and fatalities. In comparison with adults, the central nervous system of children/adolescents may be more vulnerable to the activity of these molecules, hence raising even further the levels of health-related concerns. More research is needed to provide evidence of both short- and long-term effects of NPS, related health risks, and their addiction potential.

Characteristics of deaths associated with kratom use.

BACKGROUND: Kratom (Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. AIMS: This study details the characteristics of such fatalities and provides a 'state-of-the-art' review. METHODS: UK cases were identified from mortality registers by searching with the terms 'kratom', 'mitragynine', etc. Databases and online media were searched using these terms and 'death', 'fatal*', 'overdose', 'poisoning', etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. RESULTS: Typical case characteristics (n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues. CONCLUSIONS: These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom's safety profile remains only partially understood; toxic and fatal levels require quantification.

An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions.

BACKGROUND: Although originally marketed as safe alternatives to the habit-forming benzodiazepines, growing numbers of zaleplon, zolpidem, and zopiclone ("Z-drugs") clinical concerns relating to their potential of abuse, dependence, and withdrawal have been reported over time. We aimed here at assessing these issues analyzing datasets of adverse drug reactions provided by the European Medicines Agency through the EudraVigilance system. METHODS: Analyzing the adverse drug reactions databases of each Z-drug, descriptive analyses have been performed on cases and proportional reporting ratios (PRRs) computed. RESULTS: An overall number of 33 240 (e.g., 23 420 zolpidem; 9283 zopiclone; and 537 zaleplon) misuse-, abuse-, dependence-, and withdrawal-related adverse drug reactions, corresponding to some 6246 unique patients given Z-drugs, were here identified. Cases were studied and described, including demographic characteristics and clinical data such as concomitant drugs, doses, routes of administration, and outcomes of the reactions (being fatalities recorded). Considering PRR values and in comparison with zopiclone, zolpidem was more frequently involved in both misuse/abuse and withdrawal issues. Zolpidem and zopiclone presented with the same dependence risk, but zopiclone was most involved in overdose adverse drug reactions. Compared with zaleplon, zopiclone presented higher dependence and overdose-related issues but slightly lower misuse/abuse and withdrawal PRR values. CONCLUSION: Current data may only represent a gross underestimate of the real prevalence of Z-drug misuse. Caution should be exercised when prescribing those molecules, especially for patients with psychiatric illnesses and/or history of drug abuse. We recommend the need to invest in proactive pharmacovigilance activities to better and promptly detect, understand, and prevent any possible misuse potential of prescribed medications.

Psychedelic Fauna for Psychonaut Hunters: A Mini-Review.

Currently different classes of psychoactive substances are easily available for abuse, including several hundred novel psychoactive substances (NPS). Some of these drugs occur naturally in plants and animals or are chemically modified from plant or animal compounds and have been abused by humans over millennia. Recently, the occurrence of a new "drug culture" (e.g., psychonauts) who consume a great variety of NPS with hallucinogenic/psychedelic properties, facilitated the development of a new "psychedelic trend" toward the consumption of substances contained in some species of animals ("psychedelic fauna"). The present review aims at providing an overview of the most commonly abused "psychedelic animals," by combining a dual search strategy coming from online psychonauts' experiences and English literature searches on the PubMed/Medline Google Scholar databases. A multilingual qualitative assessment on a range of websites and online resources was performed in order to identify a list of animals who possess some psychoactive properties and could be abused by humans for recreational purposes. Several species are implicated (i.e., ants, amphibians, fish). Routes of administration depend on the animal, substance included, metabolism, toxicity and individual, social and cultural variability. Online purchase and access are easy through tourism-related search strategies ("frog trip," "help of charmer snake," "religious trip").

Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review.

Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies.

An index of fatal toxicity for new psychoactive substances.

An index of fatal toxicity for new psychoactive substances has been developed based solely on information provided on death certificates. An updated index of fatal toxicity (Tf), as first described in 2010, was calculated based on the ratio of deaths to prevalence and seizures for the original five substances (amphetamine, cannabis, cocaine/crack, heroin and 3,4-methylenedioxymethylamphetamine)*. These correlated well with the 2010 index. Deaths were then examined for cases both where the substance was and was not found in association with other substances. This ratio (sole to all mentions; S/A) was then calculated for deaths in the period 1993 to 2016. This new measure of fatal toxicity, expressed by S/A, was well-correlated with the index Ln (Tf) of the original reference compounds. The calculation of S/A was then extended to a group of new psychoactive substances where insufficient prevalence or seizure data were available to directly determine a value of Tf by interpolation of a graph of Tf versus S/A. Benzodiazepine analogues had particularly low values of S/A and hence Tf. By contrast, γ-hydroxybutyrate/γ-butyrolactone, α-methyltryptamine, synthetic cannabinoid receptor agonists and benzofurans had a higher fatal toxicity.

Deaths in the Lesbian, Gay, Bisexual and Transgender United Kingdom Communities Associated with GHB and Precursors.

BACKGROUND: Misuse of gammahydroxybutrate (GHB) and its prodrugs gammabutyrolactone (GBL) and 1,4 butanediol (1,4-BD) has increased greatly since the early 1990s, particularly amongst lesbian, gay, bisexual and transgender (LGBT) individuals in recreational and sexual settings, e.g. 'chemsex'. OBJECTIVE AND METHOD: This paper presents an overview of GHB pharmacotoxicology and provides analyses of cases in the LGBT population associated with the use of these substances extracted from the UK's National Programme on Substance Abuse Deaths database, to which notification is voluntary. RESULTS: From 1995 to September 2013, 21 GHB/GBL-associated fatalities were reported. None involved 1,4-BD. Typical victims were: Male (100%); White (67%), young (mean age 34 years); employed (90%); with a drug misuse history (81%). Most deaths were accidental (67%) or related to recreational drug use (19%), the remaining (potential) suicides. The majority of fatalities (83%) occurred in private residences, typically following recreational use; others occurred in specific 'gay'-oriented locales including clubs and saunas. Three London boroughs accounted for 62% of all notified deaths, reflecting the concentration of both resident and visiting 'gay' individuals. However, this may be an artefact of the voluntary nature of the data submission procedure in particular areas. GHB/GBL alone was implicated in 10% of fatalities. The following substances were implicated either alone or in combination in the remaining cases (percentages may add to more than 100%): cocaine (38%); alcohol (33%); amphetamines (29%); ecstasy (29%); diazepam (24%); ketamine (24%); mephedrone (24%). Post-mortem blood levels: mean 660 (range 22 - 2335; S.D. 726) mg/L. CONCLUSION: Significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, stimulants, and ketamine. Risk of death is increased due to their CNS-depressant properties. Of these, 'chemsex' drugs such as cocaine, mephedrone and ketamine are of note. More awareness is needed in the 'gay' community about risks associated with the consumption of such substances.