The mystery behind the apprehensions of the selective cannabinoid receptor type-2 agonist BZO-HEXOXIZID (MDA-19) as a drug of abuse.

PURPOSE: MDA-19 or BZO-HEXOXIZID (N'-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-benzohydrazide), in a more recent nomenclature, was first synthesized in 2008 as a selective type-2 cannabinoid receptor (CB2) agonist due to its potential to treat neuropathic pain. In Brazil, this substance was identified in a series of 53 apprehensions between September 2021 and February 2022. Nevertheless, what intrigues toxicologists is that BZO-HEXOXIZID does not exert significant type-1 cannabinoid receptor (CB1) agonism-which is responsible for the well-known psychoactivity of Δ-9-tetrahydrocannabinol. Thus, the objective of this work is to report the first apprehension and identification of BZO-HEXOXIZID in Brazil and to discuss pharmacologically the possible reasons why a CB2 agonist has been incorporated to the illicit market. METHODS: Suspected seized samples were sent to the Laboratory of the Scientific Police of the State of Sao Paulo. After the screening, samples were confirmed for the presence of BZO-HEXOXIZID using chromatography gas-mass spectrometry, Fourier-transform infrared spectroscopy and nuclear magnetic resonance techniques. RESULTS: Of the 53 samples analyzed, 25 contained only BZO-HEXOXIZID and 28 with mixtures, of which 11 with the CB1 agonist ADB-BUTINACA. Other substances were found in association such as cocaine and caffeine. CONCLUSIONS: BZO-HEXOXIZID was detected in a series of seized materials for the first time in Brazil. Nevertheless, there are still unanswered questions regarding the use of this selective CB2 agonist as a drug of abuse.

Synthetic cannabinoid receptor agonists profile in infused papers seized in Brazilian prisons.

PURPOSE: Synthetic cannabinoid receptor agonists (SCRAs) are a class of varied compounds that mimic the effects of natural cannabinoids found in cannabis. Because they have a wide range of diverse structures, they vary widely in their potency. The abuse of new psychoactive substances (NPS) in prisons was reported in many European countries and in the USA. In the present study, we have described the identification of SCRAs in 56 infused paper sheet samples, seized mainly in Brazilian prisons between 2016 and 2020. METHODS: The materials were seized by local or federal law enforcement and analyzed by São Paulo State Police or Brazilian Federal Police using gas chromatography-mass spectrometry, attenuated total reflection-Fourier transform infrared spectroscopy, liquid chromatography-high-resolution mass spectrometry or nuclear magnetic resonance spectrometry. RESULTS: Most of these samples (87.5%) were seized in 2019-2020; seven different SCRAs were identified in samples, and the most frequently identified substances were MDMB-4en-PINACA (23.6%) and 5F-MDMB-PICA (36.4%), the newest SCRAs emerging recently. CONCLUSIONS: As observed in Europe and the USA, Brazil also shows the prevalence of indazole-3-carboxamides and indole-3-carboxamides among SCRAs seizures in the prison system. This phenomenon is spreading all over the world at this moment. These data on the prevalence could help to alert judicial authorities to shutting down the introduction of NPS, including SCRAs, into prisons to ensure safety and security for avoiding health risks of prisoners and staff, leading to positive effects in this population. To our knowledge, this is the first demonstration of SCRAs smuggling into prisons in Latin America.

Lucy is back in Brazil with a new dress.

Lucy in the Sky with Diamonds, a John Lennon song that was a hit in the 1960s, was born amidst a social context enlightened by lysergic acid diethylamide (LSD). In Brazil, both the drug and the song were very popular at the time, although it gradually mitigated. Nevertheless, while the song remains out of the spotlight, LSD derivatives are currently gaining attention with the rising of the new psychoactive substances (NPS). With this new presentation, the drug is returning to Brazil after a few decades and herein we report and discuss the first cases of an LSD prodrug seized in our country. Nine suspected blotter paper samples were seized by the Sao Paulo State Police in different cities of the State. Gas chromatography-mass spectrometry (GC-MS), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and liquid chromatography coupled with electrospray ionization-mass spectrometry (LC-ESI-MS) analyses were utilized to confirm the identity of the LSD derivative. The compound was identified as 4-acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52 or 1A-LSD) and no other active substance was detected in all samples. The identity of the unknown compound found in seized blotter papers has been successfully confirmed as an LSD prodrug, ALD-52, which was not controlled by Brazilian legislation. The arrival of a new type of designer drug in Brazil is in support by other reports, although those are still scarce and should not be overlooked. Altogether, these findings indicate the rising of a new NPS strategy that merits proper discussion.

Determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 and 33 compounds from eight different drug classes in whole blood by LC-MS/MS.

INTRODUCTION: Most bioanalytical LC-MS/MS methods are developed for determination of single drugs or classes of drugs, but a multi-compound LC-MS/MS method that can replace several methods could reduce both analysis time and costs. The aim of this study was to develop a high-throughput LC-MS/MS method for determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth 16:0/18:1) and 33 other compounds from eight different drug classes in whole blood. METHODS: Whole-blood samples were prepared by 96-well supported liquid extraction (SLE). Chromatographic separations were performed on a biphenyl core shell column with a mobile phase consisting of 10 mM ammonium formate, pH 3.1 and methanol. Each extract was analyzed twice by LC-MS/MS, injecting 0.4 µL and 2 µL, in order to obtain narrow and symmetrical peaks and good sensitivity for all compounds. Stable isotope-labeled internal standards were used for 31 of the 34 compounds. RESULTS: A 96-well SLE reversed phase LC-MS/MS method for determination of PEth 16:0/18:1 and 33 other compounds from eight different drug classes was developed and validated. By using an organic solvent mixture of isopropanol/ methyl tert-butyl ether (1:5, v:v), all compounds, including the polar and ampholytic compounds pregabalin, gabapentin and benzoylecgonine, was extracted by 96-well SLE. DISCUSSION/CONCLUSION: For the first time an LC-MS/MS method for the determination of alcohol biomarker PEth 16:0/18:1 and drugs and metabolites from several different drug classes was developed and validated. The developed LC-MS/MS method can be used for high-throughput analyses and sensitive determinations of the 34 compounds in whole blood.

Alcohol Consumption and Violent Deaths in the City of Sao Paulo in 2015.

Background: Excessive alcohol consumption is a serious public health issue, because drunkenness affects critical judgment and self-control, making people more vulnerable to violence and accidents, with thus a potential association between alcohol consumption and violent deaths. Objective: To assess the association between alcohol consumption and violent deaths in the city of Sao Paulo, Brazil, in 2015, and its relationship with gender, age, cause of death and blood alcohol concentration (BAC) of victims. Methods: A cross-sectional retrospective study was conducted by collection of data from 2,882 victims of violent deaths subjected to examination of BAC from the archives of the Institute of Legal Medicine of the State of Sao Paulo, Brazil. Results: Alcohol was detected in blood samples of 27.06% of the victims and mean BAC levels were 1.92 ± 1.24 g/L. The mean age of the victims was 33.49 ± 15.19 years. The majority of the victims were male (84.14%) and the prevalence of positive BAC was higher amongst men (28.74%) than women (18.16%). Homicide was the most prevalent cause of death in the sample (36.57%), but there were a higher proportion of traffic accidents victims with positive BAC (32.01%), as well as higher BAC levels in these victims (46.77% in the range of 1.6-2.5 g/L). Conclusions: The results obtained in this study support a potential association between alcohol consumption and violent deaths in the city of Sao Paulo, mainly in traffic accidents victims.

Loaded dice: A game theory analysis of drunk driving laws in Brazil.

OBJECTIVE: The aim of the study was to evaluate whether the current legislation would encourage drunk drivers to refrain from taking a breathalyzer and thus avoid jail time. METHOD: Brazilian traffic laws currently have 3 possible punishments for drivers suspected of driving under the influence: A fine and suspension of license for 12 months if the breathalyzer result is under 0.3 mg/L (by law; a result up to 0.33 mg/L would receive the same punishment due to a later regulatory document) but positive; the same punishment for refusal to take a breathalyzer test; and up to 3 years of jail time and license cancellation if over 0.3 mg/L. Analysis was done using decision tree analysis as well as game theory to evaluate the rational choice for drunk drivers according to possible financial loss. RESULTS: The authors have found that the rational choice for a drunk driver is not taking the breathalyzer test to avoid heavier penalties. This, in turn, contributes to the inefficacy of the law. CONCLUSION: The authors have also calculated that the fine for refusing should be around 2.5 times higher so that the economic equilibrium would shift toward encouraging drivers to take the test. This should also be accompanied by other incentives to promote safe behavior while driving.

Alcohol-related traffic accidents with fatal outcomes in the city of Sao Paulo.

AIMS: The aims of the present study were to characterize fatal traffic accident victims in a major urban center in Brazil and their association with alcohol consumption. METHODS: Cross-sectional study of 907 fatal traffic accident victims in Sao Paulo, in 2005. RESULTS: Adult males between the ages of 25 and 54 represented the majority of cases with positive blood alcohol concentrations (BAC). Overall, males had a higher proportion of BAC and mean BAC than females. Pedestrians, particularly those with no detectable BAC, were typically older than other victims. Most accidents (total and BAC-positive) happened on weekends between midnight and 6 a.m. Considering all victims, 39.4% were positive (BAC over 0.1g/l). When only drivers (automobile, motorcycle and bicycle) were evaluated, 42.3% had BAC over the legal limit (0.6g/l). CONCLUSIONS: Alcohol is associated with nearly half of all traffic accident deaths in the city of Sao Paulo, especially for days and times associated with parties and bars (weekends between 12 a.m. and 6 a.m.).

Neuropsychological assessment of current and past crack cocaine users.

BACKGROUND: Cognitive changes due to crack cocaine consumption remain unclear. METHODS: For clarification, 55 subjects were assigned to three groups: control group, crack cocaine current users, and ex-users. Participants were submitted to Mini-Mental State Examination (MMSE) and tasks evaluating executive functioning and verbal memory. Mood state was also measured. Intergroup comparisons were carried out. RESULTS: Control group performance on the MMSE was better than that of users and ex-users. Verbal memory performance for logical memory of users was impaired. Ex-users scored lower on DSST and Trail Making Test (Part B). CONCLUSION: Chronic crack cocaine use seems to disrupt general cognitive functioning (MMSE), verbal memory, and attentional resources, but findings suggest that some of these effects could be reversed by abstinence.

Alcohol consumption in homicide victims in the city of São Paulo.

AIMS: To assess the association between alcohol use and victimization by homicide in individuals autopsied at the Institute of Legal Medicine in São Paulo, Brazil. DESIGN: Cross-sectional study. SETTING: Excessive consumption of alcohol is a serious public health issue and a major factor in triggering violent situations, which suggests a strong association between alcohol ingestion and becoming a victim of homicide. PARTICIPANTS: Data from 2042 victims of homicides in 2005 were obtained from medical examiner reports. MEASUREMENTS: The victim's gender, age, ethnicity and blood alcohol concentration (BAC) were collected. The method of death and homicide circumstances, as well as the date, time and place of death were also studied. FINDINGS: Alcohol was detected in blood samples of 43% of the victims, and mean BAC levels were 1.55 +/- 0.86 g/l. The prevalence of positive BAC levels was higher among men (44.1%) than women (26.6%), P < 0.01. Firearms caused most of the deaths (78.6%), and alcohol consumption was greater among victims of homicide by sharp weapons (P < 0.01). A greater proportion of victims with positive BAC were killed at weekends compared to weekdays (56.4 and 38.5%, respectively; P < 0.01), and the correlation between homicide rates and the average BAC for the central area of the city was positive (r(s) = 0.90; P < 0.01). CONCLUSIONS: These results highlight alcohol as a contributing factor for homicide victimization in the greatest urban center in South America, supporting public strategies and future research aiming to prevent homicides and violence related to alcohol consumption.