A Comparative Analysis of Two Commonly Used FDA-Approved Immunoassays for Fentanyl Detection.

BACKGROUND: Given the opioid epidemic, fentanyl screening in urine has become increasingly important. Immunoassays remain the most common screening methodology due to the high throughput and ease of integration into automated chemistry systems. The fentanyl ARK II from Ark Diagnostics is a widely used immunoassay, while a novel fentanyl assay called FEN2 by Lin-Zhi has become available on the Roche platform. Here, we evaluate and compare their performance. METHODS: Four hundred and thirty-four urine samples were analyzed for fentanyl across the Lin-Zhi FEN2 and ARK II assays on the Cobas c502 platform. Samples were analyzed immediately upon request for drug of abuse screening or frozen for subsequent analysis. For confirmation testing, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a limit of detection of 1 ng/mL for fentanyl/norfentanyl was used. Any sample with either fentanyl or norfentanyl above the LC-MS/MS cutoff was deemed positive. RESULTS: The ARK II had 11 false negatives and 7 false positives, while the Lin-Zhi FEN2 had 12 false negatives and 2 false positives. This resulted in ARK II having a sensitivity and specificity of 90.4% and 97.8% respectively, while Lin-Zhi FEN2 had a sensitivity and specificity of 89.5% and 99.4%. CONCLUSIONS: Both the ARK II and Lin-Zhi FEN2 immunoassays detected fentanyl well. Overall, the Lin-Zhi assay had slightly better specificity than ARK II, in our data set. While some discrepant results were observed between the 2 immunoassay systems, most occurred near the immunoassay detection cutoffs.

Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial.

Importance: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC. Objective: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation). Design, Setting, and Participants: This double-blind, placebo-controlled parallel randomized clinical trial was conducted from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California, San Diego. Participants were aged 21 to 55 years and had used cannabis in the past month. Data were analyzed from August 2021 to April 2023. Intervention: Participants were randomized 1:1:1 to placebo (0.02% THC), 5.9% THC cannabis, or 13.4% THC cannabis smoked ad libitum. Main Outcome and Measures: The primary end point was law enforcement officer determination of FST impairment at 4 time points after smoking. Additional measures included officer estimation as to whether participants were in the THC or placebo group as well as driving simulator data. Officers did not observe driving performance. Results: The study included 184 participants (117 [63.6%] male; mean [SD] age, 30 [8.3] years) who had used cannabis a mean (SD) of 16.7 (9.8) days in the past 30 days; 121 received THC and 63, placebo. Officers classified 98 participants (81.0%) in the THC group and 31 (49.2%) in the placebo group as FST impaired (difference, 31.8 percentage points; 95% CI, 16.4-47.2 percentage points; P < .001) at 70 minutes after smoking. The THC group performed significantly worse than the placebo group on 8 of 27 individual FST components (29.6%) and all FST summary scores. However, the placebo group did not complete a median of 8 (IQR, 5-11) FST components as instructed. Of 128 participants classified as FST impaired, officers suspected 127 (99.2%) as having received THC. Driving simulator performance was significantly associated with results of select FSTs (eg, ≥2 clues on One Leg Stand was associated with impairment on the simulator: odds ratio, 3.09; 95% CI, 1.63-5.88; P < .001). Conclusions and Relevance: This randomized clinical trial found that when administered by highly trained officers, FSTs differentiated between individuals receiving THC vs placebo and driving abilities were associated with results of some FSTs. However, the high rate at which the participants receiving placebo failed to adequately perform FSTs and the high frequency that poor FST performance was suspected to be due to THC-related impairment suggest that FSTs, absent other indicators, may be insufficient to denote THC-specific impairment in drivers. Trial Registration: ClinicalTrials.gov Identifier: NCT02849587.

Driving Under the Influence of Cannabis: Impact of Combining Toxicology Testing with Field Sobriety Tests.

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers. METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired. RESULTS: There was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo. CONCLUSIONS: Requiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired.

Variable Delta-9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics After Cannabis Smoking in Regular Users.

BACKGROUND: Despite its federally restricted status, cannabis is widely used medicinally and recreationally. The pharmacokinetics (PK) and central nervous system (CNS) effects of tetrahydrocannabinol (THC), the major psychoactive cannabinoid, are not well understood. The objective of this study was to develop a population PK model of inhaled THC, including sources of variability, and to conduct an exploratory analysis of potential exposure-response relationships. METHODS: Regular adult cannabis users smoked a single cannabis cigarette containing 5.9% THC (Chemovar A) or 13.4% THC (Chemovar B) ad libitum. THC concentrations in whole blood were measured and used to develop a population PK model to identify potential factors contributing to interindividual variability in THC PK and to describe THC disposition. Relationships between model-predicted exposure and heart rate, change in composite driving score on a driving simulator, and perceived highness were evaluated. RESULTS: From the 102 participants, a total of 770 blood THC concentrations were obtained. A two-compartment structural model adequately fit the data. Chemovar and baseline THC (THC BL ) were found to be significant covariates for bioavailability, with Chemovar A having better THC absorption. The model predicted that heavy users-those with the highest THC BL -would have significantly higher absorption than those with lighter previous use. There was a statistically significant relationship between exposure and heart rate, and exposure and perceived highness. CONCLUSIONS: THC PK is highly variable and related to baseline THC concentrations and different chemovars. The developed population PK model showed that heavier users had higher THC bioavailability. To better understand the factors affecting THC PK and dose-response relationships, future studies should incorporate a wide range of doses, multiple routes of administration, and different formulations relevant to typical community use.

Evaluating the performance of the Roche FEN2 fentanyl immunoassay and its clinical implementation: The role of LDT-based mass spectrometry testing.

Introduction: While laboratory-developed tests (LDTs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) are widely employed to support the development of FDA-cleared drug immunoassays, their significance in the clinical implementation and evaluation of such assays is often overlooked. This paper reports on the important role of LC-MS/MS LDTs in demonstrating improved performance of the Roche FEN2 fentanyl immunoassay compared with the Thermo DRI fentanyl immunoassay. Methods: The FEN2 assay was implemented according to the manufacturer's instructions and its performance was compared to the existing DRI assay using LC-MS/MS as a reference. Clinical sensitivity and specificity were determined using 250 consecutive random patient specimens. Spiking experiments were conducted to determine cross-reactivity with 31 fentanyl analogs. Select DRI false-positive samples were analyzed by the FEN2 assay via time-of-flight mass spectrometry method (LC-QTOF). Results: The FEN2 assay showed improved clinical sensitivity compared to the DRI (98% vs 61%) in 250 consecutive patient samples due to its ability to detect norfentanyl. It also showed better clinical specificity by correctly classifying select DRI false-positive results. Upon implementation in clinical practice, the FEN2 resulted in a higher screening positivity rate than the DRI (17.3% vs 13.3%) and a greater LC-MS/MS confirmation rate of immunoassay-positive samples (96.8% vs 88.8%, respectively). Conclusion: The use of LC-MS/MS LDTs demonstrated that the FEN2 assay has greater clinical sensitivity and is less prone to false-positives than the DRI assay. These findings support the use of FEN2 in routine clinical practice and emphasize the role of mass spectrometry-based LDTs in clinical toxicology testing.

Comparison of two highly sensitive benzodiazepine immunoassay lab developed tests for urine drug testing in clinical specimens.

Background: The VALID Act is a legislative effort that, if enacted, would alter the regulatory requirements of laboratory developed tests (LDTs) used for clinical testing in the United States. Benzodiazepines, which are primarily excreted into urine as glucuronidated metabolites such as lorazepam, cross-react poorly with FDA-cleared immunoassays, leading to false-negatives. This shortfall can be addressed with LDTs created by adding glucuronidase to the immunoassay reagents producing "high sensitivity" assays that detect glucuronidated metabolites. Methods: Precision and stability of two high-sensitivity (HS) benzodiazepine immunoassays from Roche and Thermo Scientific were evaluated using manufacturer-supplied quality control (QC) material and glucuronidated QC material. The immunoassays were directly compared to an LC-MS/MS LDT benzodiazepine assay to determine clinical sensitivity/specificity using urine specimens (n = 82 for Thermo Scientific; n = 265 for Roche). The clinical impact of the HS LDT immunoassay was determined by analyzing clinical testing results 60 days before and after its implementation. Results: The precision and clinical sensitivity/specificity of the HS-Thermo Scientific and HS-Roche benzodiazepine assays were acceptable. The reagent stability of the HS-Thermo Scientific immunoassay was poor, whereas the HS-Roche immunoassay was stable. After implementation of the HS-Roche benzodiazepine immunoassay as an LDT, there was a 30-fold increase (p-value: < 0.00001) in the percentage of lorazepam confirmations. Conclusions: We demonstrate the development and validation of an immunoassay LDT with improved sensitivity for glucuronidated benzodiazepines. This LDT can detect glucuronidated benzodiazepines in clinical urine specimens and is stable for 60 days. Importantly, we were able to validate the immunoassay as an LDT by utilizing an LC-MS/MS LDT.

A User-Friendly Sample Preparation Alternative for Manual and Automated LC-MS/MS Quantification of Testosterone.

We describe an LC-MS/MS method for serum testosterone using a novel extraction media, AC Extraction Plate™ (AC Plate,Tecan Schweiz). The AC Plate principle is essentially that of a liquid-liquid extraction (LLE) but employs a stationary nonpolar phase coated on the wells of 96-well plates instead of a nonmiscible organic solvent for partitioning testosterone out of serum, leaving interfering substances behind. This low complexity sample preparation protocol has been validated for and used in production in our laboratory with both manual and automated liquid handling. The primary advantage of this method is the highly reproducible nature of an extraction method that does not require LC-MS/MS expertise or specialized extraction equipment. We modified the existing vendor application and validated the method for matrix effect, recovery, precision, trueness [accuracy relative to certified reference material (CRM)], specificity, reportable range, sample stability, various sample containers, and correlation with other methods.Method performance is excellent, with a reportable range of 4-750 ng/dL, between-day quality control coefficient of variation (CV) over 12 months of <8%, mean accuracy of <4.0% bias against CRM, no interference from hemolysis, icterus, lipemia, serum separator tube gel, or common steroids/metabolites, and mean bias of 1.3% versus 4 other LC-MS/MS testosterone methods. An investigation of calibration stability and robustness supports sparse (3 versus 6 calibrators) and/or historical calibration for routine use.

Driving Performance and Cannabis Users' Perception of Safety: A Randomized Clinical Trial.

IMPORTANCE: Expanding cannabis medicalization and legalization increases the urgency to understand the factors associated with acute driving impairment. OBJECTIVE: To determine, in a large sample of regular cannabis users, the magnitude and time course of driving impairment produced by smoked cannabis of different Δ9-tetrahydrocannabinol (THC) content, the effects of use history, and concordance between perceived impairment and observed performance. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled parallel randomized clinical trial took place from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California San Diego. Cannabis users were recruited for this study, and analysis took place between April 2020 and September 2021. INTERVENTIONS: Placebo or 5.9% or 13.4% THC cannabis smoked ad libitum. MAIN OUTCOMES AND MEASURES: The primary end point was the Composite Drive Score (CDS), which comprised key driving simulator variables, assessed prior to smoking and at multiple time points postsmoking. Additional measures included self-perceptions of driving impairment and cannabis use history. RESULTS: Of 191 cannabis users, 118 (61.8%) were male, the mean (SD) age was 29.9 (8.3) years, and the mean (SD) days of use in the past month was 16.7 (9.8). Participants were randomized to the placebo group (63 [33.0%]), 5.9% THC (66 [34.6%]), and 13.4% THC (62 [32.5%]). Compared with placebo, the THC group significantly declined on the Composite Drive Score at 30 minutes (Cohen d = 0.59 [95% CI, 0.28-0.90]; P < .001) and 1 hour 30 minutes (Cohen d = 0.55 [95% CI, 0.24-0.86]; P < .001), with borderline differences at 3 hours 30 minutes (Cohen d = 0.29 [95% CI, -0.02 to 0.60]; P = .07) and no differences at 4 hours 30 minutes (Cohen d = -0.03 [95% CI, -0.33 to 0.28]; P = .87). The Composite Drive Score did not differ based on THC content (likelihood ratio χ24 = 3.83; P = .43) or use intensity (quantity × frequency) in the past 6 months (likelihood ratio χ24 = 1.41; P = .49), despite postsmoking blood THC concentrations being higher in those with the highest use intensity. Although there was hesitancy to drive immediately postsmoking, increasing numbers (81 [68.6%]) of participants reported readiness to drive at 1 hour 30 minutes despite performance not improving from initial postsmoking levels. CONCLUSIONS AND RELEVANCE: Smoking cannabis ad libitum by regular users resulted in simulated driving decrements. However, when experienced users control their own intake, driving impairment cannot be inferred based on THC content of the cigarette, behavioral tolerance, or THC blood concentrations. Participants' increasing willingness to drive at 1 hour 30 minutes may indicate a false sense of driving safety. Worse driving performance is evident for several hours postsmoking in many users but appears to resolve by 4 hours 30 minutes in most individuals. Further research is needed on the impact of individual biologic differences, cannabis use history, and administration methods on driving performance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02849587.

Mass Spectrometry-Based Detection of Beta Lactam Hydrolysis Enables Rapid Detection of Beta Lactamase Mediated Antibiotic Resistance.

OBJECTIVE: Antibiotic resistance by beta lactamase expression is a serious and growing threat. We aimed to determine whether beta-lactamase activity is detectable in urine specimens to enable faster identification of resistance. METHODS: Urine specimens from patients with extended spectrum beta lactamase (ESBL)-expressing urinary infections were incubated with beta lactam antibiotics. Beta lactam hydrolysis was determined by mass spectrometry methods. RESULTS: Ceftriaxone hydrolysis was observed in 45 of 45 ESBL-containing specimens from patients not treated with a beta lactamase inhibitor before specimen collection. Ceftriaxone hydrolysis was not observed in 108 of 108 non-ESBL-containing specimens. Spiking studies show that beta lactam hydrolysis can be observed within 30 minutes. Beta lactam hydrolysis is evidenced by mass spectrometry preceded by either liquid chromatography or matrix-assisted laser desorption ionization specimen processing methods. CONCLUSION: Clinically significant beta lactamase activity is detectable directly from urine specimens. The described methods would enable the detection of beta lactam resistance 24 to 48 hours sooner than culture based methods.

Emergency Department Management of Chest Pain With a High-Sensitivity Troponin-Enabled 0/1-Hour Rule-Out Algorithm.

OBJECTIVES: The analytical sensitivity of high-sensitivity cardiac troponin T (hsTnT) assays has enabled rapid myocardial infarction rule-out algorithms for emergency department (ED) presentations. Few studies have analyzed the real-world impact of hsTnT algorithms on outcomes and operations. METHODS: Comparison of ED length of stay (LOS) and 30-day outcomes (return to ED, inpatient admission, and mortality) for patients presenting with chest pain during 2 separate 208-day periods using a 0/1-hour hsTnT-enabled algorithm or fourth-generation TnT. RESULTS: Discharge, 30-day readmission, and 30-day mortality rates were not significantly different with fourth-generation TnT vs hsTnT. Thirty-day return rates were significantly decreased with hsTnT (17.4% vs 14.9%; P < .01). For encounters with TnT measured at least twice and resulting in discharge, median ED LOS decreased by 61 minutes with the use of hsTnT (488 vs 427 minutes; P < .0001). Median time between first and second TnT results decreased by 82 minutes with hsTnT (202 vs 120 minutes; P < .0001), suggesting that the 0/1-hour algorithm was incompletely adopted. CONCLUSIONS: Implementation of the hsTnT algorithm was associated with decreased 30-day return rates and decreased ED LOS for a subset of patients, despite incomplete adoption of the 0/1-hour algorithm.

Qua-Alluding to the Past: A Case of Methaqualone Analog Ingestion.

Methaqualone, known previously under the brand name Quaalude, is a Schedule I sedative hypnotic drug that may cause neurotoxicity in overdose, characterized by somnolence, hyperreflexia and muscular hyperactivity. We present a case of a 21-year-old male who reportedly ingested methaqualone in addition to insufflation of street cocaine. He subsequently developed hypoxia, hyperreflexia, myoclonus, and altered mental status. His laboratory results were notable for the presence of methemoglobinemia, which was most likely due to a cocaine contaminant. Laboratory analysis of the alleged methaqualone pills identified the substance as SL-164, a dichlorinated methaqualone analog. Urine toxicology results were positive for SL-164 (and presumed metabolites) as well as for cocaine and tetrahydrocannabinol metabolites. The patient was treated with supplemental oxygen and a benzodiazepine (lorazepam) and observed in the Emergency Department (ED) until his symptoms resolved. This case highlights current community access to methaqualone analogs. The case also focuses on laboratory techniques used to identify the methaqualone analog.

SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated. METHODS: The ability of 4 commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 patients who were SARS-CoV-2 PCR positive, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 patients who were SARS-CoV-2 negative. Serology results were compared to a cell-based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay. RESULTS: The Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received 2 doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme NAbs assay correlated with the PSV SARS-CoV-2 median infective dose (ID50) neutralization titers (R2 = 0.70), while correlation of the Roche S-antibody assay was weaker (R2 = 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received 2 doses of the Moderna vaccine (ID50, 597) compared to individuals who received a single dose (ID50, 284). CONCLUSIONS: The Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.

A Rapid Assay for SARS-CoV-2 Neutralizing Antibodies That Is Insensitive to Antiretroviral Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike pseudotyped virus (PSV) assays are widely used to measure neutralization titers of sera and of isolated neutralizing Abs (nAbs). PSV neutralization assays are safer than live virus neutralization assays and do not require access to biosafety level 3 laboratories. However, many PSV assays are nevertheless somewhat challenging and require at least 2 d to carry out. In this study, we report a rapid (<30 min), sensitive, cell-free, off-the-shelf, and accurate assay for receptor binding domain nAb detection. Our proximity-based luciferase assay takes advantage of the fact that the most potent SARS-CoV-2 nAbs function by blocking the binding between SARS-CoV-2 and angiotensin-converting enzyme 2. The method was validated using isolated nAbs and sera from spike-immunized animals and patients with coronavirus disease 2019. The method was particularly useful in patients with HIV taking antiretroviral therapies that interfere with the conventional PSV assay. The method provides a cost-effective and point-of-care alternative to evaluate the potency and breadth of the predominant SARS-CoV-2 nAbs elicited by infection or vaccines.

Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers.

Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆9-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids' concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by liquid chromatography with tandem mass spectrometry for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent compared to occasional users, whereas there were no significant differences in OF Cmax. Blood THC remained detectable (≥5 ng/mL) at the final sample collection for 14% of individuals who smoked either the 5.9 or 13.4% THC cigarette, whereas 54% had detectable THC in OF when applying the same cutoff. Occasional and frequent cannabis users' profiles were compared, THC was detectable for significantly longer duration in blood and OF from frequent users. Detection rates between frequent and occasional users at multiple per se cutoffs showed larger differences in blood versus OF. Understanding cannabinoid profiles of frequent and occasional users and the subsequent impact on detectability with current drug per se driving limits is important to support forensic interpretations and the development of scientifically supported driving under the influence of cannabis laws.

Diagnostic Value of Procalcitonin in Transplant Patients Receiving Immunosuppressant Drugs: A Retrospective Electronic Medical Record-Based Analysis.

OBJECTIVES: To evaluate concentrations of procalcitonin (PCT) in transplant recipients receiving immunosuppressive therapy compared with nonimmunosuppressed patients. METHODS: We analyzed a data set of 9,500 inpatient encounters to compare levels of PCT and other biomarkers of infection (C-reactive protein [CRP], WBC count, and absolute neutrophil count [ANC]) between immunosuppressed and nonimmunosuppressed cohorts. We also assessed the correlation between PCT and clinical variables in immunosuppressed patients. RESULTS: Patients receiving immunosuppressive drugs had significantly higher levels of maximal and minimal PCT compared with the nonimmunosuppressed patients (P < .0001 and P = .0019, respectively). However, CRP levels, WBC count, and ANC were significantly lower in immunosuppressed patients compared with the nonimmunosuppressed patients (P = .0003, P < .0019, and P = .0001, respectively). CONCLUSIONS: Our results from real-world data demonstrated that PCT dynamics remain intact despite immunosuppressive therapy, in contrast to other biomarkers such as CRP, WBC, and ANC. In addition, higher PCT levels are associated with systemic infections and reflect disease severity.

Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats.

RATIONALE: Cannabidiol (CBD) reduces craving in animal models of alcohol and cocaine use and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal. However, preclinical evaluation of its efficacy is still lacking. OBJECTIVES: The goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence. METHODS: Male and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for 2 weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for 2 weeks, starting 1 week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps received sesame oil injections (double vehicle) or the highest dose of CBD 30 mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded. RESULTS: CBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD. The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30 mg/kg/day) did not alter these results. CONCLUSIONS: This preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine cessation may be beneficial.