Global Drug Research Articles

In-home cannabis smoking more prevalent than in-home tobacco smoking among 2019 Global Drug Survey respondents

Purpose of the ResearchEarly evidence from studies of home smoking policies suggests that in-home cannabis smoking is more often allowed than in-home tobacco smoking, but there are not yet data on whether cannabis is more often smoked in the home compared to tobacco, or whether in-home cannabis and tobacco smoking differs by usage status. Using cross-sectional data from over 100,000 sentinel drug users from 17 countries, we compared cannabis and tobacco smoking in the homes of Global Drug Survey 2019 respondents who currently used cannabis only, tobacco only, both tobacco and cannabis, or neither. Principal ResultsComplete data on cannabis and tobacco use and in-home smoking were available for 107,272 adults (average age = 30 ± 12, 34% women, countries with the three highest response rates; Germany = 32%, USA = 10%, New Zealand = 9%). In total, 53.6% and 50.6% of respondents reported past-year cannabis and tobacco smoking in their home respectively. Stratifying respondents into current cannabis-only users, tobacco-only users, dual users, and non-users, past-year in-home cannabis smoking was more prevalent (78.8%) among cannabis-only users than was in-home tobacco smoking (67.9%) among tobacco-only users. Among dual users, past-year in-home cannabis smoking (82.8%; 95%CI = 80%-86%) was higher than in-home tobacco smoking (75.9%; 95%CI = 69%–81%; p < 0.001). In-home cannabis and tobacco smoking was similar among non-users (20.2% and 20.5%, respectively). Major ConclusionsPast-year in-home cannabis smoking was more prevalent than tobacco smoking in the homes of participants who used cannabis and/or tobacco, supporting our speculation that in-home cannabis smoking might be more socially acceptable than in-home tobacco smoking.

Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p’s < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.

Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34.

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36–0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.

How the Global COVID-19 Pandemic Brought Drug and Vaccine Development into the Public Mainstream

Pharmaceutical development was at the forefront of efforts to prevent infection with the SARS-CoV-2 virus as well as to treat its often-devastating effects. Drug development, and its multifaceted and multi-disciplined activity toward effective vaccines and drugs, became part of everyday news. I review several key areas of vaccine and drug development that were brought into the public mainstream over the evolution of the pandemic. These include the unprecedented speed of vaccine discovery and development, issues uncovered from early clinical studies, and regulatory concepts that were highlighted throughout the development process. Among these was the importance of pharmacovigilance as each new agent was rapidly deployed to a mostly eager public. Critical challenges around production, packaging, and procurement of product for patient use were often centre stage. Finally, the ever-important need to transition not only from scientific concept to vaccine and drug, but from their authorized and approved use to their implementation in health systems to insure the intended effects both in individuals and populations.

New Books across the Disciplines

New Books across the Disciplines

Evaluation of availability, price, and affordability of cardiovascular, diabetes, and global medicines in Abuja, Nigeria.

ObjectiveTo assess the availability, price, and affordability of cardiovascular, diabetes, and global medicines in Abuja, Nigeria.MethodsA cross-sectional survey involving 27 private pharmacies, 13 public pharmacies, and 25 private hospital pharmacies in Abuja was conducted using the standardized World Health Organization/Health Action International methodology. The availability percentage for each pharmacy sector and each medicine was analyzed. The median price ratio (MPR) (ratio of the median price to the international reference prices) of the medicines were evaluated accordingly. Affordability was assessed by calculating the number of days’ wages the lowest-paid unskilled government worker required to purchase a month worth of the standard treatment for a chronic condition.ResultsThe availability of cardiovascular (CV) medicines ranged from 28.4% (in private hospital pharmacies) to 59.9% (in private pharmacies). There was mixed variability in the mean availability of Originator Brands (OBs) and Lowest Priced Generics (LPGs) anti-diabetic drugs with the highest availability being OBs 36% and LPGs 40.2%, in private pharmacies and public pharmacies, respectively. The availability of global drugs ranged from 49.7% in private hospitals to 68.8% in private pharmacies. Two cardiovascular and four global medicines had greater than 80% availability across the pharmaceutical sectors. The median price ratio for OBs and LPGs was 9.60 and 1.72 for procurement, it was 8.08 and 2.60 in private pharmacies, 13.56 and 2.66 in public hospitals, and 16.38 and 7.89 in private hospitals. The percentage markup on LPG was 49.4% in public hospitals, 51.4% in private pharmacies, and 323% in private hospitals. Only nine medicines in both public hospitals and private pharmacies and two in the private hospital pharmacies required less than the daily wage of the lowest-paid government worker.ConclusionThe availability of cardiovascular, diabetes, and global medicines was below 80% across the different pharmaceutical sectors in Abuja and the medicines were unaffordable. Although the prices were generally exorbitant, private pharmacies offered the best options in terms of availability, pricing, and affordability of medicines. Therefore, the results of this study emphasize the pertinence of enforcing policies that facilitate the availability, pricing, and affordability of cardiovascular, diabetes, and global medicines.

Changes in Purchases for Intensive Care Medicines During the COVID-19 Pandemic: A Global Time Series Study

BackgroundDrug supply disruptions have increased during the COVID-19 pandemic, especially for medicines used in the ICU. Despite reported shortages in wealthy countries, global analyses of ICU drug purchasing during COVID-19 are limited.Research QuestionHas COVID-19 impacted global drug purchases of first-, second-, and third-choice agents used in intensive care?Study Design and MethodsWe conducted a cross-sectional time series study in a global pharmacy sales dataset comprising approximately 60% of the world’s population. We analyzed pandemic-related changes in units purchased per 1,000 population for 69 ICU agents. Interventional autoregressive integrated moving average models tested for significant changes when the pandemic was declared (March 2020) and during its first stage from April through August 2020, globally and by development status.ResultsRelative to 2019, ICU drug purchases increased by 23.6% (95% CI, 7.9%-37.9%) in March 2020 (P < .001) and then decreased by 10.3% (95% CI, –16.9% to –3.5%) from April through August (P = .006). Purchases for second-choice medicines changed the most, especially in developing countries (eg, 29.3% increase in March 2020). Despite similar relative changes (P = .88), absolute purchasing rates in developing nations remained low. The observed decrease from April through August 2020 was significant only in developed countries (–13.1%; 95% CI, –17.4% to –4.4%; P < .001). Country-level variation seemed unrelated to expected demand and health care infrastructure.InterpretationPurchases for intensive care medicines increased globally in the month of the COVID-19 pandemic declaration, but before peak infection rates. These changes were most pronounced for second-choice agents, suggesting that inexpensive, generic medicines may be purchased more easily in anticipation of pandemic-related ICU surges. Nevertheless, disparities in access persisted. Trends seemed unrelated to expected demand, and decreased purchasing from April through August 2020 may suggest overbuying. National and international policies are needed to ensure equitable drug purchasing during future pandemics.

Stuck in Traffic: Conflicting Regimes of Global Drug Regulation

Stuck in Traffic: Conflicting Regimes of Global Drug Regulation

Causes, Nature and Toxicology of Fentanyl-Analogues Associated Fatalities: A Systematic Review of Case Reports and Case Series.

ObjectiveMortalities due to fentanyl derivatives are on the rise with novel fentanyl analogues and still emerging on the global illicit drug market. They are highly potent and very fatal in low doses, yet there has been a lack of systematic research surrounding this subject. This review aims to assess the causes, nature, and toxicology of fatalities associated with fentanyl analogues.MethodsFive databases: Scopus, Embase, Medline, PubMed and Google Scholar were searched from inception to October 2020 to identify case studies and case series reporting fentanyl analogue-related fatalities. Two independent reviewers screened and selected the articles followed by the data extraction from each article, which included demography, route of administration, causes and nature of death, and the fentanyl analogue implicated. All articles were then subject to quality assessment tools developed by the Joanna Briggs Institute (JBI). A narrative synthesis was undertaken.ResultsThe initial data search yielded 834 articles, only 14 of which met the inclusion criteria – this included nine case reports and five case series. Of the 1079 fentanyl-analogue related deaths reported, the majority of them occurred in the US (n=1044, 96.8%). The majority of fatalities were male (n=766, 71%), white (n=884, 87%) and in the age ranges 25–34 and 35–44 years (30.5% and 29.6%, respectively). The most common route of administration was intravenous (n=319, 66%) and the manner of death was almost exclusively accidental (99.7%). The predominant cause of death was fentanyl-analogue toxicity (n=292, 85.4%) and involved mixed drug toxicity (n=47, 13.7%). The mean post-mortem fentanyl analogue concentration was 31.6 ng/mL.ConclusionMost fatalities were reported in the US involving young white males. Overdose through intravenous administration and by mixed drug toxicities with other opioids were the major causes of death. Deaths reported in peer-reviewed literature were relatively less than those reported by real-world data.

ASHP Foundation's forecast report feels more relevant than ever this year

ASHP Foundation's forecast report feels more relevant than ever this year

Where and What You Drink Is Linked to How Much You Drink: An Exploratory Survey of Alcohol Use in 17 Countries

Background This paper aimed to explore the differences in subjective experiences of intoxication depending on drinking location and drink type. Methods: Data came from 32,194 respondents to The Global Drug Survey (GDS) 2015, an annual, cross-sectional, online survey. Respondents selected their usual drinking location (home alone: home with partner/family: house parties: pubs/bars or clubs) and usual drink (wine; beer/cider/lager; spirits or alcopops/coolers). They indicated how many drinks they required to reach three stages of intoxication (feeling the effects; an ideal stage of intoxication; and the tipping point) and how frequently they reached each stage. Results: Drink type affected grams of alcohol reported to reach the tipping point: 109 gm wine, 127 gm alcopops, 133 gm of beer, and 134 gm of spirts. Respondents who drank at home alone, or in clubs reached their tipping point more frequently compared to other locations. Conclusions: Where people drink, and the type of alcohol they drink, affected the amount of alcohol reported to reach different stages of intoxication. Understanding why different drinking locations, and drink types lead to a need for greater consumption to reach an ideal state of drunkenness, such as social cues from other people who drink, may enable people to reduce their drinking.

Can health technology assessments assist the global campaign against poverty?

Although a key tenant of the Sustainable Development Goals is to achieve universal health coverage, the global drug gap persists—over a third of the global population lack access to essential medicines. Without access to affordable drugs, people have worse health outcomes, higher medical expenses, and productivity loss, pushing them into poverty. Health technology assessments (HTAs) offer an opportunity to decrease the global drug gap and increase access to essential medicines by overcoming barriers to medicine access. These barriers include drug procurement, drug affordability for payers and patients, a patient's ability to obtain essential medicines, and health system capacity. Using HTAs can therefore close the global drug gap by increasing access to affordable essential medicines. In turn, people have better health outcomes, spend less money on medical care, and can have better productivity. Ultimately, use of HTAs can lift the population out of poverty and force fewer people into poverty by creating better health outcomes at affordable prices.

Monitoring geographical differences in illicit drugs, alcohol, and tobacco consumption via wastewater-based epidemiology: Six major cities in Turkey

A national wastewater-based epidemiology (WBE) monitoring campaign has been initiated to determine the trends in drug consumption in Turkey since 2019. This study aimed to present the wastewater monitoring results for four periods in 2019 for six major cities with 17 wastewater treatment plants. The study investigated heroin (HER), amphetamine (AMP), methamphetamine (METH), cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA), cannabis, alcohol, and tobacco to understand the temporal and geographical drug consumption trends. The results indicated a trend of regular cannabis use in all the cities. Considering geographical variations, the drug usage trends were not homogeneous within the country for any of the investigated drugs, except cannabis. HER consumption was predominant in Denizli (1042.48 mg/1000 inh/day), while İzmir and Antalya (154.10 and 79.56 mg/1000 inh/day, respectively) topped for COC consumption. Aydın had the highest consumption levels of AMP (90.03 mg/1000 inh/day) and METH (358.13 mg/1000 inh/day), while MDMA consumption was the highest in Samsun (157.64 mg/1000 inh/day). Tobacco consumption was high in Aydın (8791.69 mg/1000 inh/day) and Antalya (5375.17 mg/1000 inh/day), whereas alcohol consumption was higher in Bursa than in the other cities (53434.61 mL/1000 inh/day). There were no statistically significant differences in the weekend consumption levels of the investigated drugs among these six cities. Although this study included the results of 1 year of consumption monitoring, the data confirms internationally published information on the drug trafficking routes of conventional drugs in this region, especially the Heroin-Balkan route. Results from further sampling will enable accurate evaluation of global drug consumption and trafficking, in addition to alcohol and tobacco use.

Global Drug Prohibition in Local Context: Heroin, Malaria, and Harm

Cairo’s Qasr El Aini Hospital regularly received opiate addicts in poor health, but a startling new development in April 1929 captured the attention of Dr. Alexander Gordon Biggam, Director of the Medical Unit. Patients with a history of injecting heroin were being admitted with high fevers, and diagnored with falciparum malaria. Shocked by the prevalence of the disease, which appeared confined to networks of injection drug users, Dr. Biggam hypothesized—correctly—that the disease was being spread through contamined blood in shared syringes. “If the theory of the production of this malignant malarial infection amongst the heroin addicts is correct,” he concluded, “we are faced with a problem of considerable importance to the inhabitants of Cairo.”1 In the winter of 1932, a similar novel outbreak of malaria among injecting heroin users occupied Dr. Guy Henry Faget, an Assistant Surgeon at the United States Marine Hospital in New Orleans, a facility serving primarily merchant seamen. “If the hypodermic syringe must be accepted as a means of conveying malaria among narcotic addicts,” Dr. Faget warned, “then a new chapter in the epidemiology of this disease has been opened.”2

The appearance and increase in the quantity and proportion of the clinical research coordinator\u2019s service fee in drug clinical trial research fund and its impact on trial quality

ObjectiveThe changes of absolute value and relative value of clinical research coordinator service fee and its influence on the quality of drug clinical trial were analyzed.MethodsThis study compared the amount and structural changes of drug clinical trial costs in before 3 years and after 3 years of self-examination and inspection initiated by the China Food and Drug Administration, identified the increase number and composition of each individual cost of a clinical trial research funds which including clinical research coordinator service fee, investigator labor fee, subjects examination fee, subjects traffic subsidy, documents management fee, drug management fee, etc.ResultThe most significant appearance of increase in volume and proportion was the clinical research coordinator service fee. From the initial few to the global multicenter tumor drug clinical trials RMB31,624 or 34.92% of the proportion and domestic multicenter tumor drug clinical trials RMB16,500, accounted for 33.74%.DiscussionIt has become common for more money to be spent on clinical trials to be accompanied by improved quality, but the occurrence and continuous increase of clinical research coordinator service fee were divided into two aspects, On the one hand, the quality of clinical trials was promoted by the large amount of low-skill trivial work undertaken by clinical research coordinator; on the other hand, the quality of clinical trials was undermined by the fact that clinical research coordinator did too much treatment evaluation work that should have been done by the investigator.ConclusionThe clinical research coordinators’ access standards, pre-employment training and examination, job and performance evaluation, in addition to the SMO specification management and avoiding malicious competition between the industry, are important factors in the quality assurance of drug clinical trials.

Efficacy of a Fixed-Dose Combination of Ibuprofen and Acetaminophen Compared With Individual Monocomponents in Adult Male Subjects With Endotoxin-Induced Fever: A Randomized Controlled Trial

PurposeThis study evaluated antipyretic efficacy and onset of a novel fixed-dose combination (FDC) of ibuprofen (IBU; 250 mg) and acetaminophen (APAP; 500 mg) compared with placebo and IBU or APAP monocomponents. MetThis single-center, randomized, double-blind, placebo-controlled, full-factorial study was conducted in healthy males aged 18 to 55 years with pyrexia induced by intravenous administration of reference standard endotoxin (RSE). After attainment of an oral temperature ≥38.1°C, subjects were randomized 3:3:3:1 to a double-blind single oral dose of FDC IBU/APAP 250 mg/500 mg, APAP 500 mg, IBU 250 mg, or placebo. Oral temperature was measured every 10 minutes for 2 hours, then every 30 minutes until 8 hours postdose. Time-weighted sum of temperature differences from baseline to 8 hours (WSTD0–8) after study medication administration was the primary efficacy end point. Secondary end points included WSTD scores from 0 to 2 hours, 0 to 4 hours, 0 to 6 hours, and 6 to 8 hours; time to return to “normal” temperature; time to rescue medication use; and global drug evaluation. Safety was assessed via adverse events (AEs). FindingsTwo hundred ninety subjects were randomized; 273 were included in the primary efficacy analysis. WSTD0–8 was significantly better for FDC IBU/APAP 250 mg/500 mg (P = 0.002), IBU 250 mg (P = 0.030), and APAP 500 mg (P = 0.023) versus placebo; there were no significant differences between active treatments. For WSTD0–2, only the FDC was statistically significant versus placebo (P = 0.004). All active treatments were significantly better (P < 0.05) for WSTD0–4 and WSTD0–6 versus placebo; there were no differences in WSTD6–8 between cohorts. Temperature returned to normal during the 8-hour treatment period in ∼50% of subjects in each cohort. Only 1 subject (IBU cohort) took rescue medication. Post hoc analyses at early time points revealed significant treatment differences favoring FDC versus placebo and IBU for the WSTD from baseline during the 50- to 110-minute posttreatment window; for WSTD from baseline during the 80- to 110-minute posttreatment window, FDC provided significant treatment differences versus placebo and both monocomponents. Overall, 223 (76.9%) of 290 subjects experienced AEs related to RSE; only 2 subjects experienced treatment-related AEs (FDC, rash; placebo, ear pain). ImplicationsAlthough the primary end point was not met, these results suggest that FDC IBU/APAP 250 mg/500 mg provides effective antipyresis with a faster onset versus equal doses of IBU and APAP alone. ClinicalTrials.gov identifier: NCT02761980.

An investigation on the association between sodium glucose co-transporter 2 inhibitors use and acute pancreatitis: A VigiBase study.

To characterize acute pancreatitis (AP) related to sodium glucose co-transporter 2 inhibitors and to investigate this relationship through disproportionality analysis in an international pharmacovigilance database. We analyzed all AP reports for canagliflozin, dapagliflozin and/or empagliflozin from the WHOs Global adverse drug reactions database VigiBase® up to July 2019. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR) and information component (IC) for each of the gliflozins. AP cases were reports containing at least one of 11 previously selected preferred terms. Gliflozin exposure was considered for all reports with at least one gliflozin as suspected/ interacting drug. Of the 19 834 180 individual case safety reports in VigiBase, in 600 reports containing 618 AP group reactions, gliflozins were suspected/ interacting drugs. Men were affected in 52.3% of the cases and 59.6% of the patients were in the 45-64 years age group. The reporters were in 417 cases healthcare professionals. Most of the reactions were reported for canagliflozin (59.7%), followed by empagliflozin (21%) and dapagliflozin (19.2%) and were serious (98.6%). Most of the reactions' outcomes (84% of the patients) were favorable. Ketoacidosis was frequently associated with the AP (21.3%). Significant PRR and IC were found for pancreatitis and pancreatitis acute for all three gliflozins, pancreatitis necrotizing for canagliflozin and empagliflozin and pancreatitis relapsing for empagliflozin. Most of the AP cases were serious and with favorable outcome. We identified possible alternative causes for AP, like concomitant medication, hypertriglyceridemia, and cholelithiasis and a frequent association with ketoacidosis. We found a significant association between AP and the use of canagliflozin, dapagliflozin, and empagliflozin that would need further investigation.

Continuous manufacture of hydroxychloroquine sulfate drug products via hot melt extrusion technology to meet increased demand during a global pandemic: From bench to pilot scale

During pandemics and global crises, drug shortages become critical as a result of increased demand, shortages in personnel and lockdown restrictions that disrupt the supply chain. The pharmaceutical industry is therefore moving towards continuous manufacturing instead of conventional batch manufacturing involving numerous steps, that normally occur at different sites. In order to validate the use of large-scale industrial processes, feasibility studies need to be performed using small-scale laboratory equipment. To that end, the scale-up of a continuous process and its effect on the critical quality attributes (CQAs) of the end product were investigated in this work. Hydroxychloroquine Sulphate (HCQS) was used as the model drug, Soluplus® as a model polymeric carrier and both horizontal and vertical twin screw extruders used to undertake this hot melt extrusion (HME) study. Seven formulations were processed using a small-scale horizontal extruder and a pilot-scale vertical extruder at various drug loadings, temperature profiles and screw speeds. When utilising a horizontal extruder, formulations with the highest drug load and processed at the lowest screw speed and temperature had the highest crystallinity with higher drug release rates. Upon scale-up to a vertical extruder, the crystallinity of the HCQS was significantly reduced, with less variation in both crystallinity and release profile across the different extrudates. This study demonstrates improved robustness with the pilot-scale vertical extruder compared to lab-scale horizontal extruder. The reduced variation with the vertical extruder will allow for short increases in production rate, with minimum impact on the CQAs of the final product enabling high-performance continuous manufacturing with minimum waste of raw materials. Finally, this research provides valuable information for the pharmaceutical industry in accessing continuous technologies for the manufacture of pharmaceutical products, allowing for efficient utilisation of resources upon scale-up and mass production during global pandemics and drug shortages.

Designer Benzodiazepines: A Review of Toxicology and Public Health Risks.

The rising use of designer benzodiazepines (DBZD) is a cat-and-mouse game between organized crime and law enforcement. Non-prohibited benzodiazepines are introduced onto the global drug market and scheduled as rapidly as possible by international authorities. In response, DBZD are continuously modified to avoid legal sanctions and drug seizures and generally to increase the abuse potential of the DBZD. This results in an unpredictable fluctuation between the appearance and disappearance of DBZD in the illicit market. Thirty-one DBZD were considered for review after consulting the international early warning database, but only 3-hydroxyphenazepam, adinazolam, clonazolam, etizolam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, phenazepam and pyrazolam had sufficient data to contribute to this scoping review. A total of 49 reports describing 1 drug offense, 2 self-administration studies, 3 outpatient department admissions, 44 emergency department (ED) admissions, 63 driving under the influence of drugs (DUID) and 141 deaths reported between 2008 and 2021 are included in this study. Etizolam, flualprazolam flubromazolam and phenazepam were implicated in the majority of adverse-events, drug offenses and deaths. However, due to a general lack of knowledge of DBZD pharmacokinetics and toxicity, and due to a lack of validated analytical methods, total cases are much likely higher. Between 2019 and April 2020, DBZD were identified in 48% and 83% of postmortem and DUID cases reported to the UNODC, respectively, with flualprazolam, flubromazolam and etizolam as the most frequently detected substances. DBZD toxicology, public health risks and adverse events are reported.

Comparing intentions to reduce substance use and willingness to seek help among transgender and cisgender participants from the global drug survey

AimsTo describe and compare psychoactive substance misuse help-seeking among transgender (trans) and cisgender (cis) participants from a large multi-national cross-sectional survey.BackgroundTrans people experience stressors related to their minority status which have been associated with increased rates of psychoactive substance use and related harm. Despite this, there is a paucity of evidence relating to the treatment needs of trans people who use psychoactive substances, beyond a small body of literature describing a culture of transphobic hostility in general substance misuse services. This paper aims to describe and compare psychoactive substance misuse help-seeking among trans and cis participants from a large multi-national cross-sectional survey.MethodOver 180,000 participants, recruited from the world's largest annual survey of drug use - the Global Drug Survey (GDS) - during 2018 and 2019, reported use of a range of psychoactive substances in the preceding 12 months. Five gender groups (118,157 cis men, 64,319 cis women, 369 trans men, 353 trans women and 1,857 non-binary people) were compared, using Chi-square and z-tests with Bonferroni correction, on items relating to the desire to use less psychoactive substances and the need to seek help to achieve this. Respondents from GDS 2018 were also assessed for substance dependence. Binary logistic regression was used to compare gender groups on self-reported substance dependence to frame the help-seeking analyses.ResultTrans respondents (n = 1,710) to GDS 2018 were significantly more likely than cis respondents to report use of illicit substances (OR = 1.66-2.93) and dependence on cannabis (OR = 2.39), alcohol (OR = 3.28) and novel psychoactive substances (OR = 4.60). In the combined GDS 2018 and 2019 dataset, there were no significant differences between trans (n = 2,579) and cis (n = 182,476) participants on the desire to reduce substance use. However, among those who did report wanting to use less, non-binary people and trans women were most likely to want help to achieve this.ConclusionTrans respondents reported a greater need for help with reducing substance use than cis respondents. Given the deficit of specialist services for psychoactive substance users who are trans, there is a need for a more thorough understanding of the barriers and facilitators to their engagement in general substance misuse services. In the interim, substance misuse service providers require education about gender minority status to help meet the needs of trans clients.