Background: While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy.Methods: We used a large administrative database to determine whether psychiatric medications are continued during pregnancy and predictors of continued medication treatment.Results: Of 2,672,656 women included in our analysis, 86,454 (3.1%) filled a pre-pregnancy prescription for an anxiolytic or antidepressant medication within 3 months of estimated conception. Of women who filled a pre-pregnancy prescription, 49.4%, 26.1%, and 20.1% filled subsequent prescriptions in the 1st, 2nd, and 3rd trimesters. Discontinuation rates ranged by pharmaceutical agent, from 16% for fluoxetine to 71% for alprazolam. White women and women over 25 were more likely to continue anxiolytic and antidepressant treatment during pregnancy.Conclusion: Because untreated and under-treated mental health conditions are linked to adverse maternal outcomes, high discontinuation rates may have important implications for maternal health.

Information on the pattern of acute poisonings in hospitals of Birjand city, Iran, is limited. This study aimed to address this knowledge gap by examining the admissions in a major poisoning center in eastern Iran. This cross-sectional study included patients admitted to the Imam Reza Hospital in Birjand over 12 months. Medical records of the poisoned patients were reviewed, and the study variables were used for data analysis. During the study period, 534 cases of acute poisonings were evaluated. The patient's ages ranged from 12 to 84 years, with a high rate of poisonings between 15 and 35 years. The female predominance in poisoning cases was 52.1%. Most cases of poisonings occurred in spring, and the common route of exposure was oral (93.1%). The incidence of poisoning in married couples, uneducated patients, and residents of urban areas was 56.5%, 90.1%, and 74.6%, respectively. Patients with a previous medical history experienced addiction and psychiatric disorders. Intentional poisoning accounted for 23.4% of acute poisoning cases referred to the hospital in the current study. The main groups of toxicants were pharmaceutical products (48.1%), narcotics (25.8%), chemical products (10.1%), envenomation (7.1%), and alcohol (1.7%). The mean hospital stay was 2.5 ± 3.0 days, and the final treatment outcome was complete recovery, except for one patient intoxicated by warfarin and alprazolam. Our results indicate that the high toxicity cases were related to pharmaceutical product and opioids abuse, especially methadone (8.4%), alprazolam (7.9%), clonazepam (7.5%), and acetaminophen (9.9%) taken orally and more commonly happened at home. Due to the high rate of deliberate poisonings, especially among young adults and students, monitoring drug distribution and exceptional attention to mental health should be seriously considered by national health authorities to prevent suicide attempts.

The current meta-analysis searched the literature connected to different tranquilizers used to treat elderly people and assessed it in terms of dose, types of outcomes and adverse effects, to determine a safe and acceptable tranquilizer and its optimal dose. A systematic literature review was undertaken for randomized controlled trials, case-control, retrospective and prospective studies on the use of tranquilizers in elderly patients, using PubMed, Ebsco, SCOPUS and Web of Science. PICOS criteria were used to select studies, and pertinent event data was collected. This meta-analysis includes 16 randomized control trials spanning the years 2000 to 2022, using the data from 2224 patients. The trials that were included used various tranquilizers such as diazepam, alprazolam, temazepam and lorazepam, and indicated high treatment efficacy and low adverse effects. With a p-value of 0.853 for Egger's test and 0.13 for Begg's test, the current meta-analysis shows a minimal probability of publication bias. A recent meta-analysis supports the use of tranquilizers in older people to treat sleeplessness, epilepsy or anxiety, but only at modest doses, because large doses are harmful and produce numerous withdrawal symptoms.

Missourians are dying of fentanyl poisoning at an unprecedented rate. We identified growth areas in Missouri for fatal fentanyl encounters in rural and western counties. Though the deaths occur for a multitude of reasons, a growing trend adds to the surge in fentanyl fatalities: poisonings from counterfeit pills. The tablets are often labeled with brand names for alprazolam or oxycodone, but may contain only fentanyl at a dangerous level. Teenagers find counterfeit pills all too easily via social media. Believing they have found an easy way to obtain a quick high or relief of minor pain and anxiety, they take the pill alone in their bedroom, with no possibility of reversing a fatal fentanyl dose. There is a wide range of respiratory depression from illicit drugs containing fentanyl. We reviewed the physiologic respiratory response to drugs containing fentanyl that varies with genetics and the unpredictable amount of fentanyl contained in illicit drugs.

The current study was designed to investigate the feasibility of incorporating the water-insoluble lipophilic drug Alprazolam (Alp) into solid lipid nanoparticles (SLNs) to offer the combined benefits of the quick onset of action along with the sustained release of the drug. Therefore, compritol-based alprazolam-loaded SLNs (Alp-SLNs) would provide early relief from anxiety and sleep disturbances and long-lasting control of symptoms in patients with depression, thereby enhancing patient compliance. The optimized Alp-SLNs analyzed by DLS and SEM showed consistent particle size of 92.9 nm with PI values and standard deviation of the measurements calculated at <0.3 and negative surface charge. These characteristic values demonstrate the desired level of homogeneity and good physical stability of Alp-SLNs. The SLNs had a good entrapment efficiency (89.4%) and high drug-loading capacity (77.9%). SEM analysis revealed the smooth spherical morphology of the SLNs. The physical condition of alprazolam and absence of interaction among formulation components in Alp-SLNs was confirmed by FTIR and DSC analyses. XRD analysis demonstrated the molecular dispersion of crystalline alprazolam in Alp-SLNs. The in vitro release study implied that the release of Alp from the optimized Alp-SLN formulation was sustained as compared to the Alp drug solution because Alp-SLNs exhibited sustained release of alprazolam over 24 h. Alp-SLNs are a promising candidate to achieve sustained release of the short-acting drug Alp, thereby reducing its dosing frequency and enhancing patient compliance.

Alprazolam is a triazolobenzodiazepine which is most commonly used in the short-term management of anxiety disorders, often in combination with antipsychotics. The four human members of the CYP3A subfamily are mainly responsible for its metabolism, which yields the main metabolites 4-hydroxyalprazolam and α-hydroxyalprazolam. We performed a comparison of alprazolam metabolism by all four CYP3A enzymes upon recombinant expression in the fission yeast Schizosaccharomyces pombe. CYP3A4 and CYP3A5 show the highest 4-hydroxyalprazolam production rates, while CYP3A5 alone is the major producer of α-hydroxyalprazolam. For both metabolites, CYP3A7 and CYP3A43 show lower activities. Computational simulations rationalize the difference in preferred oxidation sites observed between the exemplary enzymes CYP3A5 and CYP3A43. Investigations of the alprazolam metabolites formed by three previously described CYP3A43 mutants (L293P, T409R, and P340A) unexpectedly revealed that they produce 4-hydroxy-, but not α-hydroxyalprazolam. Instead, they all also make a different metabolite, which is 5-N-O alprazolam. With respect to 4-hydroxyalprazolam, the mutants showed fourfold (T409R) to sixfold (L293P and P340A) higher production rates compared to the wild-type (CYP3A43.1). In the case of 5-N-O alprazolam, the production rates were similar for the three mutants, while no formation of this metabolite was found in the wild-type incubation.

Benzodiazepines and z-hypnotics are detected in the majority of fatal overdose cases in Norway, often in combination with other drugs of abuse, and their concentrations in peripheral blood might be important to elucidate the cause of death. In some forensic autopsies, peripheral blood is however not available. The aim of the present study was to compare concentrations of benzodiazepines and z-hypnotics in five alternative matrices to assess whether these concentrations are comparable to concentrations in peripheral blood. A total of 109 forensic autopsy cases were included. Peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle and vitreous humour from each case were analysed using UHPLC-MS/MS. We were able to detect clonazepam, 7-aminoclonazepam, flunitrazepam, 7-aminoflunitrazepam, nitrazepam, 7-aminonitrazepam, diazepam, nordiazepam, oxazepam, alprazolam, midazolam, zopiclone and zolpidem in all the analysed matrices. Concentrations measured in vitreous humour were generally much lower than those of peripheral blood for all compounds except zopiclone. 7-amino metabolite concentrations were high compared to the parent compounds, although less so for the muscle samples. In muscles, concentrations of the parent nitrobenzodiazepines were higher than in peripheral blood, but for the other compounds, concentrations in muscle showed good correspondence with peripheral blood. Both cardiac blood and pericardial fluid were viable alternative matrices for peripheral blood, although a larger variation and a tendency for higher concentrations in pericardial fluid was observed. This study shows that cardiac blood, psoas and lateral vastus muscle samples and pericardial fluid can give comparable concentrations to peripheral blood for benzodiazepines and z-hypnotics, while vitreous humour was less suitable. The concentrations in alternative matrices must, however, be interpreted carefully.

Studies have shown that psychotropic drugs change rat behavior in the elevated plus-maze test (EPM). This study investigated whether static magnetic fields could alter alprazolam-induced rat behavior in the EPM. 66 male Wistar rats (270-300 g weight) were assigned to one of the following groups: Sham Magnetic + Saline (SMS), North Pole + Saline (NPS), South Pole + Saline (SPS), Sham magnetic + alprazolam (SMA), NP + alprazolam (NPA), and SP + alprazolam (SPA). After five days of static magnetic stimulation (3200 Gauss), they received alprazolam or saline (1 mg/kg), and their behavior was evaluated. Two-way ANOVA and Holm-Sidak post-hock were used, with a significant P value of <0.05. The SMA and NPA groups showed an increased number of entries and time in the open arms compared with the SMS group. SPA showed a decrease in these measures when compared to SMA [F(2,61) = 6.43 and F(2,61) = 3.72, respectively]. The SMA and NPA groups showed increased head dipping and end-arm activity compared with the SMS group. SPA showed a decrease in these measures when compared to SMA [F(2,61) = 3.37 and [F(2,61) = 4.72, respectively]. These results show that the south magnetic pole of a static magnetic field blocked the alprazolam effect in the space-time variables of the open arms and ethological anxiolytic-like behavior in the EPM.

In March 2020, the WHO announced the COVID-19 pandemic, which has been ongoing for over 2 years. To stop the spread of the virus, the governments of many countries decided to introduce reasonable social restrictions that were suitable for pandemic waves. This led to radical changes in people's lives, especially among students, who are very active in society. Before COVID-19, being of student age was associated with the highest frequency of stimulants use. It is important to note that drugs are taken disparately in various areas. Therefore, using the Computer-Assisted Web Interview type of study, the impact of the pandemic on the use of alcohol, cannabinoids, psychostimulants (e.g., amphetamine, methamphetamine, ecstasy) and sedatives (e.g., zolpidem, zopiclone, alprazolam, lorazepam, etc.) was assessed among students from European countries. The questionnaire included single- and multiple-answer questions. The first part concerned sociodemographic questions, while the second included questions about the use of stimulants in the last 3 months prior to participation in the study. Distribution of the survey covered the period from 31 January 2016 to 30 April 2021. A total of 17,594 European students participated in the study. The vast majority of participants were women (80.4%) and students of non-medical universities (77.2%) living in Eastern European countries (86.1%). Of all students, 15,613 (89.6%) reported alcohol drinking, 2538 (14.1%) the use of cannabinoids, 650 (3.6%) psychostimulants, and 2252 (12.5%) sedatives in the past three months. It has been shown that women are far less likely to use alcohol (OR 0.81), psychostimulants (OR 0.44) and cannabinoids (OR 0.49), while they are more likely to use sedatives (OR 1.41). During the COVID-19 pandemic, the consumption of alcohol (OR 0.55) and psychostimulants (OR 0.72) decreased and that of sleep medications increased (OR 1.17). To conclude, the COVID-19 pandemic influenced the pattern of stimulants used by students in European countries. The restriction of social interactions contributed to the decrease in the consumption of alcohol and psychostimulants but increased the use of sedatives and the frequency of their use. Women were found to use sedatives more often, while men preferred to drink alcohol and use cannabinoids or psychostimulants. It has also been shown that students of Central and Eastern Europe more often use alcohol and sedatives, while in Southern European countries psychostimulants and cannabinoids are preferred.

The purpose of this review study was to sum up the main recent advances reported in the scientific literature about the detection of common drugs of abuse in biological samples upon their collection by dried blood spot devices. The most recent, innovative and fully validated methods for the qualitative and/or quantitative detection of common drugs of abuse are reported, including alprazolam, clonazepam, diazepam, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methyl-enedioxyethylamphetamine, amphetamine, methamphetamine, cocaine, tetrahydrocannabinol, 6-monoacetylmorphine, morphine, codeine, hydromorphone, hydrocodone, oxycodone, noroxycodone, tramadol, methadone, buprenorphine, fentanyl, ketamine and their respective metabolites and γ-hydroxybutyric acid. Dried blood spot proved to be extremely promising for routine analysis of forensic cases, although large-scale experiments on real samples need to be performed to confirm the emerging advantages of the technique and remove the potential limitations still affecting its widespread application.

An effective adsorbent was synthesised from nanographene oxide for the removal of the alprazolam drug from the water sample solution. The dispersive solid-phase extraction method was used with α-pyridylamine grafted nanographene oxide to extract and analyse little amounts of alprazolam in biological materials. Before beginning the experimental analysis process, it is critical to use a simple and accessible sample preparation approach. In the current study, a technique for preconcentration and measurement of trace quantities of alprazolam in aqueous samples was introduced. The pH of extraction, the amount and type of elution solvent and the period of extraction were all tuned in the alprazolam analysis technique. Analytical parameters such as the concentration factor, the limit of detection of the technique and relative standard deviation (%) were achieved as 20, 8.0 µg L-1 and 2.4%, respectively.

Onychophagia is a habitual nail-biting disorder, usually associated with mental or emotional diseases. It affects 20-30% of the population in all age groups. Human bites have the potential to become serious injuries due to high virulence in the human oral flora and may often require hospital admission, antibiotics and even debridement in the operating room. Thus, repetitive nail biting has the potential to be limb-threatening if not treated early and appropriately. We present a 49-year-old Spanish-speaking gentleman, with a past medical history of repetitive nail biting secondary to severe anxiety, major depression disorder, bilateral hand neuropathy secondary to diabetes mellitus (DM) type 2 who was initially admitted to the hospital due to cellulitis of the fingers with suspected osteomyelitis in the right hand. Anxiety was being treated by psychiatrist with paroxetine however, given no improvement and prolonged follow-ups, the primary care physician (PCP) added hydroxyzine and scheduled alprazolam in an attempt to minimize symptoms. Despite these efforts, patient continued with nail biting. On initial physical exam, the patient had a lack of fingernails and multiple wounds at various stages of healing across all digits. The distal and middle phalanges of the third right digit showed increased erythema and swelling and band tightening. Patient was started on broad-spectrum antibiotics. Initial radiography of the right hand was concerning for osteomyelitis which was later confirmed with Magnetic Resonance Imaging (MRI). Infectious disease specialist agreed on a course of cefepime, vancomycin and metronidazole. On admission, hand surgeon did not see a need for amputation and patient was treated conservatively. Due to minimal improvement after six days on IV antibiotics, patient underwent fasciotomy of the flexor compartment of the right middle finger after patient rejected hand surgeon's recommendation for amputation. He was discharged to a skilled nursing facility where he was to continue intravenous antibiotics for an additional four weeks. The vulnerable patient population of South Texas is predominately Hispanic, Spanish-speaking and uninsured. It is imperative to treat psychiatric disorders early to prevent complications, however, given the low numbers of psychiatrists in the Rio Grande Valley and even fewer who speak Spanish it is not unusual to find an appointment in more than six months. In this case, we observe how a trivial everyday behavior can lead to limb-threatening complications if not treated early and appropriately.

Enhancement of skin permeation of drugs is affected by the simultaneous co-permeation of excipients that hinder the predictivity of in vitro tests. The collaborative effects of two permeation enhancers (ethanol and d-limonene) of a lipophilic drug (alprazolam) have been simultaneously assessed in human skin under different in vitro conditions: integrated setups of diffusion cell experiments with selective concentration gradients of permeants (asymmetric) or without (symmetric) have been combined with coadministration dosages (all-in-one) at different concentrations or short-time skin pretreatment to scrutiny this mutual performance. Findings: Drug permeation is increased under moderated supersaturation but reaches a stationary level above 33 % of its solubility. Ethanol in absence of a concentration gradient increases ca.5 times basal drug permeation. Limonene until 20 % permeates human skin proportionally to its donor concentration but its effect does not depend on ethanol in symmetric conditions and is based on skin imbibition rather than on a carry-on effect. Simultaneous permeation of ethanol and limonene reaches a stationary state after 1.5 h, enough time to achieve maximal enhancement of alprazolam permeation. Additive enhancement is based on ethanol solubilisation maximized by skin saturation of terpene. Complementary analyses of skin disruption published in the literature are in line with these assessments and consolidate them.

Somatization refers to the condition in which psychological distress is shown in the form of somatic symptoms such as persistent headache, nausea, gastrointestinal discomfort, etc. Various predisposing factors, including familial such as high expressed emotion, poor parental care, genetic, biological, and demographic which includes age and gender, cognitive such as learning disabilities, psychiatric such as depression, anxiety, post-traumatic stress disorder, social, etc., play an essential role in saturation of the disease. During the time of the COVID-19 pandemic, psychological distress increased in the patients infected with the coronavirus due to some the factors such as social distancing from loved ones, lack of physical exercise, loss of income, loneliness due to quarantine, etc. Therefore, management and treatment of the disorder became essential, especially in coronavirus-infected patients, as it may lead to an increase in complications of the disease. Many studies have been conducted to identify the proper way to manage the condition. Treatments include pharmacological therapy and psychosocial interventions. Pharmacological therapy includes using various antidepressants, hypnotics, and sedatives such as benzodiazepines. For the treatment, mirtazapine is a secure and reliable antidepressant. Another drug, trizolobenzodiazepine adinazolam, was also very useful in treating patients. In some randomized experiments, alprazolam significantly outperformed amitryptiline in reducing the symptoms. Psychosocial interventions include sessions such as cognitive behavioral therapy (CBT), mindfulness-based cognitive therapy, relaxation training, meditation, and psychological interventions such as enhancing multidimensional social help, modifying cognitive assessment, directing positive coping, and inspiring positive emotions.

Psychiatric drugs released by humans in wastewater have received more attention because of their potential risks for aquatic organisms. In this study, the occurrence of the two most common groups of psychiatric drugs (sedatives-hypnotics-anxiolytics and antidepressants) were evaluated in the Tehran South Municipal Wastewater Treatment Plant. All the target sedatives-hypnotics-anxiolytics (alprazolam, phenobarbital, and thioridazine) and antidepressants (fluoxetine, citalopram, sertraline, and venlafaxine) were observed in influent and secondary clarification (SC) effluent. Thioridazine (164.25 ± 218.74 ng/L) and citalopram (672.53 ± 938.56 ng/L) had the highest mean concentrations in the influent, while alprazolam (5.09 ± 2.33 ng/L) and citalopram (776.97 ± 1088.01 ng/L) had the highest concentrations in the SC effluent. The higher concentrations of the psychiatric drugs, except thioridazine, were detected in the SC effluent compared to the concentrations in the influent. The increased drugs concentrations, with negative removal efficiencies, were more distinctive in the cold season samples. Psychiatric drugs processed in the chlorination unit followed a completely different pattern compared to the drugs in the biological treatment unit. All the drugs' concentrations, except thioridazine, decreased in the chlorination unit, ranging between 27 ± 14% for alprazolam and 75 ± 10% for citalopram. However, the mean concentrations of the detected drugs were as follows: sertraline (11.96 ± 11.62 ng/L) and venlafaxine (184.94 ± 219.74 ng/L) which could cause environmental and ecological concerns.

Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L-1 and 1 to 50 mg L-1), low limit of detection (1 µg L-1), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.

Licorice, the roots and rhizomes of Glycyrrhiza glabra L., has been used as a medicinal herb, herbal adjuvant, and flavoring agent since ancient times. Recently, licorice extracts have become popular as dietary supplements used by females to alleviate menopausal symptoms. Exposure to licorice products containing high levels of glycyrrhizic acid can cause hypokalemia, but independent from this effect, preclinical data indicate that licorice can inhibit certain cytochrome P450 (P450) enzymes. To evaluate whether clinically relevant pharmacokinetic interactions of licorice with P450 enzymes exist, a phase 1 clinical investigation was carried out using a licorice extract depleted in glycyrrhizic acid (content <1%) and a cocktail containing caffeine, tolbutamide, alprazolam, and dextromethorphan, which are probe substrates for the enzymes CYP1A2, CYP2C9, CYP3A4/5, and CYP2D6, respectively. The botanically authenticated and chemically standardized extract of roots from G. glabra was consumed by 14 healthy menopausal and postmenopausal female participants twice daily for 2 weeks. The pharmacokinetics of each probe drug were evaluated immediately before and after supplementation with the licorice extract. Comparison of the average areas under the time-concentration curves (AUCs) for each probe substrate in serum showed no significant changes from licorice consumption, whereas time to reach peak concentration for caffeine and elimination half-life for tolbutamide showed small changes. According to the US Food and Drug Administration guidance, which is based on changes in the AUC of each probe substrate drug, the investigated licorice extract should not cause any clinically relevant pharmacokinetic interactions with respect to CYP3A4/5, CYP2C9, CYP2D6, or CYP1A2. SIGNIFICANCE STATEMENT: Despite generally-recognized-as-safe status, the licorice species Glycyrrhiza glabra has been associated with some toxicity. Preclinical studies suggest that G. glabra might cause pharmacokinetic drug interactions by inhibiting several cytochrome P450 enzymes. This phase 1 clinical study addressed these concerns by evaluating clinically relevant effects with respect to CYP3A4/5, CYP2C9, CYP2D6, and CYP1A2. These results showed that a standardized G. glabra extract did not cause any clinically relevant pharmacokinetic drug interactions with four major cytochrome P450 enzymes.

The combined abuse of benzodiazepines and antipsychotics has become a global problem, and to develop a highly sensitive and selective method for monitoring of benzodiazepine hypnotics and antipsychotics is urgently necessary. In this work, we established a rapid method for the simultaneous determination of benzodiazepines (diazepam, alprazolam, triazolam, and estazolam) and antipsychotic drugs (clozapine, and chlorpromazine) based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), specificity, matrix effect and carry-over effect were verified in detail. The results of the recovery and repeat experiments proved that the proposed UPLC-MS method possessed very satisfactory accuracy and precision. The LOD and LOQ of the six psychoactive substances were as low as 0.001-0.005 and 0.005-0.01 μg L-1, respectively. The proposed method was employed to analyze urine samples which were pretreated with a protein precipitation process. The potential influences of precipitants on the analysis results were evaluated statistically, and 0.1% formic acid/acetonitrile/water was selected as the optimum precipitation agent. The detection of the targets was free from matrix and carryover effects.

Clonazolam is a derivative of the Xanax active ingredient, alprazolam. Classified as a designer benzodiazepine, clonazolam availability has been rising because of its circulation on illegal internet drug markets and marginal cost in comparison to its parent analogs. Clonazolam's accessibility encourages abuse prevalence and use of designer benzodiazepines. In our case, a 14-year-old male was found unresponsive the morning after ingesting multiple tablets believed to be Xanax. Toxicology testing indicated 140 ng/mL of 8-aminoclonazolam, a clonazolam metabolite, in the decedent's system. Alprazolam was not identified. Pathological analysis determined cerebral and respiratory depression to be the mechanism of death, resulting from acute clonazolam intoxication. This case presents the first death induced by clonazolam alone. Current literature identifies a gap in designer benzodiazepine confirmatory testing and a lack of awareness within the forensic and medical communities. Knowledge of designer benzodiazepines is needed to better understand their potency and to help prevent future intoxications. We present this case to aid in the recognition of novel benzodiazepines by medical examiners and coroners, to encourage their consideration in suspected Xanax and other substance related investigations, and to be aware of the capabilities of toxicological testing to improve novel benzodiazepine identification and subsequent interpretation.

Objective: Polypharmacy increases the prevalence of potentially inappropriate drugs potentially inappropriate medications among older persons, lowering their quality of life. PIMs use can lead to higher mortality in older patients. This study aimed to compare the prevalence of PIMs in older Chinese outpatients according to the Beers criteria and the Chinese criteria and to analyze the risk factors. Second, we describe the differences between the two criteria, focusing on the inappropriate prescription of drugs in older outpatients. Methods: In Chengdu, Southwest China, a cross-sectional study was undertaken using electronic medical data from 9 general hospitals s. Outpatients above the age of 60 who were treated in the Geriatrics Center of these medical institutions were included. The 2019 Beers criteria and the 2017 Chinese criteria were used to evaluate the PIM status of older outpatients, and binary logistic regression was used to identify potential risk factors for PIMs. Results: There were 44,458 prescriptions from 2016 to 2018. The prevalence of PIMs among older outpatients was 30.05% (according to the Beers criteria) and 35.38% (according to the Chinese criteria), with statistical difference. Estazolam, hydrochlorothiazide and alprazolam were the top three PIMs in the Beers criteria, while the top three PIMs in the Chinese criteria were clopidogrel, estazolam and insulin. The prevalence of PIMs was associated with age, the number of diseases and the number of drugs. PIMs were shown to be more common in patients aged 70 and above, with more than 2 kinds of diseases and more than 4 kinds of drugs. Conclusion: PIMs were shown to be common among older outpatients in China, according to this study. The detection rate of the Chinese criteria was higher than that of the Beers criteria.

Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.

In the present work, a fast, relatively cheap, and green analytical strategy to identify and quantify the fraudulent (or voluntary) addition of a drug (alprazolam, the API of Xanax®) to an alcoholic drink of large consumption, namely gin and tonic, was developed using coupling near-infrared spectroscopy (NIR) and chemometrics. The approach used was both qualitative and quantitative as models were built that would allow for highlighting the presence of alprazolam with high accuracy, and to quantify its concentration with, in many cases, an acceptable error. Classification models built using partial least squares discriminant analysis (PLS-DA) allowed for identifying whether a drink was spiked or not with the drug, with a prediction accuracy in the validation phase often higher than 90%. On the other hand, calibration models established through the use of partial least squares (PLS) regression allowed for quantifying the drug added with errors of the order of 2-5 mg/L.

Benzodiazepines are medications used for the treatment of multiple conditions including anxiety disorders, insomnia, agitation, and seizures. They are the most prescribed psychiatric medications and the third most misused drugs among adults and adolescents in the US. This study aims to assess the patient utilization patterns and benzodiazepine use disorder among Lebanese patients. A cross-sectional study was performed on Lebanese patients presenting to the Emergency Department of the American University of Beirut Medical Center (AUBMC), between November 11th, 2019, and May 30th, 2020. Institutional review board approved the study, and an informed consent was obtained from patients. A total of 244 patients were included in the final analysis. A total of 154 (63.1%) patients were found to have benzodiazepine use disorder as per the DSM-V criteria with the majority (64%) being females and young adults aged 18 to 40 years. The most common medication was alprazolam, and anxiety was the most common reason for benzodiazepine use. The majority (88%) of patients obtained their medications using a physician's prescription. More than half of users were not satisfied with the physician's instructions and lacked knowledge about side effects and abuse potential. The high rate of benzodiazepine misuse among our young adults highlights an important public health concern that requires interventions and policy implementation.

Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.

This study evaluated the reinforcing effects of fentanyl, alone or in combination with the benzodiazepine alprazolam, in rhesus monkeys (3 females, 3 males). Subjects were trained to self-administer the opioid remifentanil (0.3 µg/kg/injection) under a progressive-ratio schedule of reinforcement. The reinforcing effects of fentanyl (0.1-10 µg/kg/injection) or alprazolam (1.0-100 µg/kg/injection) alone, or in combinations of fixed proportions (1:1, 1:3, and 3:1 fentanyl:alprazolam, with 1:1 based on the potencies of drugs alone) were evaluated in single-day test sessions (with double determinations). Dose-equivalence analysis was used to determine the extent to which fentanyl and alprazolam combinations differed from additivity. Fentanyl functioned as a positive reinforcer in all monkeys, while alprazolam was a reinforcer in 3 of 6 monkeys only. Therefore, drug combination data were grouped as "alprazolam-taking" and "non-alprazolam-taking" monkeys. For alprazolam-taking monkeys, we observed additive effects for the 3:1 and 1:3 combinations, and a significant supra-additive interaction for the 1:1 combination of fentanyl and alprazolam. For 2 of the 3 non-alprazolam-taking monkeys, the combination of fentanyl and alprazolam resulted in enhanced reinforcing effects relative to either drug alone. However, the one monkey showed primarily inhibitory, or suppressive effects, with the 3:1 dose combination resulting in a relatively modest rightward shift in the fentanyl dose-response function. In summary, our findings show that combining fentanyl and alprazolam generally result in proportion-dependent additive or supra-additive enhancements. These data raise the possibility that the prevalence of opioid-benzodiazepine polydrug abuse may reflect a unique enhancement of these drugs' reinforcing effects, although individual differences may exist. SIGNIFICANCE STATEMENT: Addressing the critical question of the degree to which benzodiazepines can modulate the abuse-related effects of opioids may provide improved pathways to treatment of this common form of polydrug addiction. In the present study, we show that combinations of the opioid fentanyl and the benzodiazepine alprazolam can be more reinforcing than either drug alone in a rhesus monkey model, suggesting that enhancement of reinforcement processes may underlie this prevalent form of polydrug use disorder.