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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To determine the lethal toxicity of five commonly-used illicit substances by relating the number of associated deaths to their availability. Methods An index of toxicity was calculated for each of five drugs [heroin, cocaine/crack, ecstasy (MDMA), amphetamine and cannabis] as the ratio of the number of deaths associated with that substance to its availability in the period 2003–2007. Three separate proxy measures of availability were used (number of users as determined by household surveys, number of seizures by law enforcement agencies and estimates of the market size). All data are related to England and Wales only. Results There was a broad correlation between all three denominators of availability. Not unexpectedly, heroin and cannabis showed, respectively, the highest and lowest toxicities. The index of fatal toxicity of MDMA was close to that of amphetamine and cocaine/crack. There was a rank correlation between this index and other measures of lethal toxicity based on safety ratios. Conclusions These results are contrary to widely-held public views of the relative fatal toxicity of MDMA. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology. [ABSTRACT FROM AUTHOR]