Impact of the COVID-19 Pandemic on HIV Test Uptake Among People Who Inject Drugs in the Context of an HIV Outbreak.

Glasgow, Scotland's largest city, has been experiencing an HIV outbreak among people who inject drugs (PWID) since 2015. A key focus of the public health response has been to increase HIV testing among those at risk of infection. Our aim was to assess the impact of COVID-19 on HIV testing among PWID in Glasgow. HIV test uptake in the last 12 months was quantified among: (1) PWID recruited in six Needle Exchange Surveillance Initiative (NESI) surveys (n = 6110); linked laboratory data for (2) people prescribed opioid agonist therapy (OAT) (n = 14,527) and (3) people hospitalised for an injecting-related hospital admission (IRHA) (n = 12,621) across four time periods: pre-outbreak (2010-2014); early-outbreak (2015-2016); ongoing-outbreak (2017-2019); and COVID-19 (2020-June 21). From the pre to ongoing period, HIV testing increased: the highest among people recruited in NESI (from 28% to 56%) and on OAT (from 17% to 54%) while the lowest was among people with an IRHA (from 15% to 42%). From the ongoing to the COVID-19 period, HIV testing decreased markedly among people prescribed OAT, from 54% to 37% (aOR 0.50, 95% CI 0.48-0.53), but increased marginally among people with an IRHA from 42% to 47% (aOR 1.19, 95% CI 1.08-1.31). In conclusion, progress in increasing testing in response to the HIV outbreak has been eroded by COVID-19. Adoption of a linked data approach could be warranted in other settings to inform efforts to eliminate HIV transmission.

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study.

PURPOSE: Cannabichromene (CBC) is a phytocannabinoid commonly found in cannabis, yet its acute post-dose pharmacokinetics (PK) have not been examined in humans. This is a secondary data analysis from a trial investigating Spectrum Yellow oil, an oral cannabis product used for medical purposes that contained 20 mg cannabidiol (CBD), 0.9 mg Δ9-tetrahydrocannabinol (THC), and 1.1 mg CBC, per 1 mL of oil. METHODS: Participants (N = 43) were randomized to one of 5 groups: 120 mg CBD, 5.4 mg THC, and 6.6 mg CBC daily; 240 mg CBD, 10.8 mg THC, and 13.2 mg CBC daily; 360 mg CBD, 16.2 mg THC, and 19.8 mg CBC daily; 480 mg CBD, 21.6 mg THC, and 26.4 mg CBC daily; or placebo. Study medication was administered every 12 h for 7 days. Plasma CBC concentrations were analyzed by a validated two-dimensional high-performance liquid chromatography-tandem mass spectrometry assay. RESULTS: After a single dose and after the final dose, the Cmax of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the tmax range was 1.6-4.3 h. Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0-t of CBD was only 6.6-9.8-fold higher than the AUC0-t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC. CONCLUSIONS: CBC may have preferential absorption over CBD and THC when administered together. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry #ACTRN12619001450101, registered 18 October 2019.

Postexposure Prophylaxis With rVSV-ZEBOV Following Exposure to a Patient With Ebola Virus Disease Relapse in the United Kingdom: An Operational, Safety, and Immunogenicity Report.

BACKGROUND: In October 2015, 65 people came into direct contact with a healthcare worker presenting with a late reactivation of Ebola virus disease (EVD) in the United Kingdom. Vaccination was offered to 45 individuals with an initial assessment of high exposure risk. METHODS: Approval for rapid expanded access to the recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine as an unlicensed emergency medicine was obtained from the relevant authorities. An observational follow-up study was carried out for 1 year following vaccination. RESULTS: Twenty-six of 45 individuals elected to receive vaccination between 10 and 11 October 2015 following written informed consent. By day 14, 39% had seroconverted, increasing to 87% by day 28 and 100% by 3 months, although these responses were not always sustained. Neutralizing antibody responses were detectable in 36% by day 14 and 73% at 12 months. Common side effects included fatigue, myalgia, headache, arthralgia, and fever. These were positively associated with glycoprotein-specific T-cell but not immunoglobulin (Ig) M or IgG antibody responses. No severe vaccine-related adverse events were reported. No one exposed to the virus became infected. CONCLUSIONS: This paper reports the use of the rVSV-ZEBOV vaccine given as an emergency intervention to individuals exposed to a patient presenting with a late reactivation of EVD. The vaccine was relatively well tolerated, but a high percentage developed a fever ≥37.5°C, necessitating urgent screening for Ebola virus, and a small number developed persistent arthralgia.

Eight weeks of sofosbuvir/velpatasvir for genotype 3 hepatitis C in previously untreated patients with significant (F2/3) fibrosis.

Twelve weeks sofosbuvir/velpatasvir (SOF/VEL) is a highly effective pan-genotypic regimen for hepatitis C. Phase 2 data suggest 8 weeks of treatment may be sufficient for previously untreated noncirrhotic patients with genotype 3 (GT3) infection. To maximize the number of patients potentially cured within a fixed treatment budget, we elected to treat such patients locally eligible for treatment (F2/3), with 8 weeks of SOF/VEL. By local protocol, treatment-naive patients with F2 (LSM > 6.9kPa < 9.5kPa) or F3 fibrosis (≥9.5kPa < 12.5kPa) were eligible for 8-week SOF/VEL treatment. Patients commencing treatment before 1 Oct 2017 were identified from the Scottish HCV database. Baseline and treatment outcome data obtained. Ninety patients were included for analysis (72 (80%) male, mean age 45 (IQR ± 8.4), 28 (31.1%) F3 fibrosis). Opioid agonist therapy (OAT) was prescribed in 82 (91.1%) patients. Of 49 patients attending Glasgow city Alcohol and Drug Services, 27 (55.1%) had evidence of recent drug use (< 3 months) including 8 (16.3%) with self-reported intravenous drug use. On an intention-to-treat basis, SVR rates were 86/90 (95.6%, 95% CI 89.0-98.8). Excluding those who prematurely discontinued treatment (n = 4), died prior to SVR testing (n = 1) or whom experienced reinfection (n = 1), per-protocol SVR rate was 84/84 (100%, 95% CI 95.7-100.0). In conclusion, eight-week SOF/VEL is highly effective in treatment-naive GT3 patients with significant fibrosis. This offers a non-protease inhibitor-based 8-week regimen which may be useful for complex drug interactions or where time-limited opportunity for treatment. In limited resource settings, reduction in drug acquisition costs may help achieve progress towards the goal of HCV elimination.

Withdrawal Symptoms From E-Cigarette Abstinence Among Adult Never-Smokers: A Pilot Experimental Study.

INTRODUCTION: Use of e-cigarettes among never-smokers has substantially increased; yet there are few descriptions of the consequences of such use. We assessed whether adult never-smokers can have withdrawal from cessation of e-cigarettes. METHODS: In an un-blinded pre-post clinical trial, 30 never-smoker daily e-cigarette users used their own nicotine-containing e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence. Participants monitored symptoms of nicotine withdrawal nightly via an Interactive Voice Response system. They attended three lab visits/week to provide expired carbon monoxide and urine samples to determine compliance. FINDINGS: Abstinence increased all the DSM5 symptoms of tobacco withdrawal and this occurred in the majority of participants. The increase in severity of withdrawal was small and rarely impaired functioning. CONCLUSIONS: Our finding suggests that withdrawal symptoms can occur in never-smokers who stop e-cigarettes abruptly. However, the severity of withdrawal appears to be small and may not be of clinical or regulatory significance. Although our sample size was small and thus replication tests of our results are indicated, it may be prudent to warn never-smokers that withdrawal symptoms may occur. IMPLICATIONS: This study indicates that withdrawal symptoms can occur in never-smokers who are daily e-cigarette users. However, the severity of withdrawal from e-cigarette abstinence in never-smokers appears to be small and may not be of clinical or regulatory significance. Given our small sample size, replication of our results is warranted. Nevertheless, it might be prudent to warn never-smokers of addiction to e-cigarettes.Clinical Trial Registration = NCT02825459.

Withdrawal Symptoms From E-Cigarette Abstinence Among Former Smokers: A Pre-Post Clinical Trial.

INTRODUCTION: The major aim of this study was to test whether abstinence from e-cigarettes causes withdrawal symptoms in former smokers. METHODS: We conducted an unblinded, within-participants, pre-post clinical trial in which 109 former smokers who were current daily electronic cigarette (e-cigarette) users used their own e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence engendered via an escalating contingency payment system. Participants monitored symptoms of nicotine withdrawal daily via an Interactive Voice Response system. They also attended three laboratory visits per week for carbon monoxide and cotinine testing to verify abstinence. RESULTS: Half of participants completely abstained for a week. All the Diagnostic and Statistical Manual, Fifth Edition (DSM-5) tobacco withdrawal symptoms, craving for e-cigarettes, craving for tobacco cigarettes, and the four possible new withdrawal symptoms (anhedonia, impulsivity, mood swings, and positive affect) increased during abstinence. Weight increased and heart rate decreased with abstinence. Symptoms showed the prototypical inverted U time pattern of a withdrawal state. The magnitude of withdrawal appeared to be somewhat less than that in a prior study of abstinent daily tobacco cigarette smokers. More severe withdrawal on the first 2 days of abstinence did not predict abstinence on the last day of the study. CONCLUSIONS: Former smokers who are daily e-cigarette users transfer physical dependence on tobacco cigarettes to dependence on e-cigarettes. The severity of withdrawal from e-cigarettes appears to be only somewhat less than that from daily tobacco cigarette use. Replication tests that include placebo controls, testing for pharmacological specificity, and including never-smokers, non-daily e-cigarette users and dual users are indicated. IMPLICATIONS: Our results indicate e-cigarettes can maintain physical dependence. This adverse effect should be included in any risk vs. benefit calculation. Also, potential and current e-cigarette users should be informed that abrupt cessation of e-cigarettes can cause withdrawal symptoms. TRIAL REGISTRATION: NCT02825459.

Chemical characterization of marijuana blunt smoke by non-targeted chemical analysis.

Background: Marijuana blunts, which are tobacco cigar wrappers filled with marijuana, are commonly smoked in the US as a means of cannabis use. The use of marijuana blunts presents toxicity concerns because the smoke contains both marijuana-related and tobacco-related chemicals. Thus, it is important to understand the chemical composition of mainstream smoke (MSS) from marijuana blunts. This study demonstrates the ability to detect and identify chemical constituents exclusively associated with blunt MSS in contrast to tobacco cigar MSS (designated as 'new exposures') through non-targeted chemical analysis.Methods: Samples collected separately from blunt MSS and tobacco cigar MSS were analyzed using two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS).Results and Discussion: Two new exposures, which likely represent only a subset of all new exposures, were identified by evaluating the data from thousands of detected signals and then confirming selected compound identities in analyses using authentic chemical standards. The two confirmed new exposures, mellein and 2-phenyl-2-oxazoline, are not cannabinoids and, to the best of our knowledge, have not been previously reported in association with cannabis, tobacco, or smoke of any kind. In addition, we detected and quantified three phenols (2-, 3-, and 4-ethylphenol) in blunt MSS. Given the toxicity of phenols, quantifying the levels of other phenols could be pursued in future research on blunt MSS.Conclusion: This study shows the power and utility of GC × GC-TOFMS as a methodology for non-targeted chemical analysis to identify new chemical exposures in blunt MSS and to provide data to guide further investigations of blunt MSS.

Prenatal Substance Use and Perceptions of Parent and Partner Use Using the 4P's Plus Screener.

Background Prenatal substance use screening is recommended. The 4 P's Plus screener includes questions on perceived problematic substance use in parents and partner that are not considered in risk stratification. Objectives This research examined the: (1) prevalence of self-reported problematic parental and partner substance use and associations with biochemically-verified prenatal substance use; (2) utility of self-reported perceptions of parent/partner substance use as proxies for prenatal substance use; and (3) degree to which the sensitivity of the 4P's Plus can be augmented with consideration of parent/partner questions in risk stratification. Methods A convenience sample of 500 pregnant women was recruited between January 2017 and January 2018. Participants completed the 4P's Plus and provided urine for drug testing. Diagnostic utility of problematic parent/partner substance use questions was assessed, then compared to the 4P's Plus used as designed, and to the 4P's Plus used with these 2 questions included in risk stratification. Results Half (51%) of respondents reported either partner or parental problematic substance use. When partner or parent problematic substance use were considered as proxies for prenatal substance use, sensitivity was 65% and specificity was 55%. When used as intended, sensitivity was 94% and specificity was 29%. Including partner/parent questions increased sensitivity to 96% but lowered specificity (19%). Partner substance use and combined partner/parent use were associated with prenatal substance use [adjusted odds ratio (aOR): 2.0 (1.2, 2.4; p = 0.006); aOR = 1.6 (1.1, 2.5, p = 0.04)]. Conclusions for Practice Sensitivity of the 4P's Plus may improve with inclusion of self-reported problematic partner/parent substance use items in risk stratification.

Cytocompatibility and Cellular Internalization of PEGylated "Clickable" Nucleic Acid Oligomers.

The recently developed synthetic oligonucleotides referred to as "click" nucleic acids (CNAs) are promising due to their relatively simple synthesis based on thiol-X reactions with numerous potential applications in biotechnology, biodetection, gene silencing, and drug delivery. Here, the cytocompatibility and cellular uptake of rhodamine tagged, PEGylated CNA copolymers (PEG-CNA-RHO) were evaluated. NIH 3T3 fibroblast cells treated for 1 h with 1, 10, or 100 µg/mL PEG-CNA-RHO maintained an average cell viability of 86%, which was not significantly different from the untreated control. Cellular uptake of PEG-CNA-RHO was detected within 30 s, and the amount internalized increased over the course of 1 h. Moreover, these copolymers were internalized within cells to a higher degree than controls consisting of either rhodamine tagged PEG or the rhodamine alone. Uptake was not affected by temperature (i.e., 4 or 37 °C), suggesting a passive uptake mechanism. Subcellular colocalization analysis failed to indicate significant correlations between the internalized PEG-CNA-RHO and the organelles examined (mitochondria, endoplasmic reticulum, endosomes and lysosomes). These results indicate that CNA copolymers are cytocompatible and are readily internalized by cells, supporting the idea that CNAs are a promising alternative to DNA in antisense therapy applications.

Cigar and Marijuana Blunt Use Among Pregnant and Nonpregnant Women of Reproductive Age in the United States, 2006-2016.

OBJECTIVES: To assess trends in prevalence of cigar and blunt use in relation to cigarette use among pregnant and nonpregnant women of reproductive age. METHODS: We used 2006 to 2016 data from the US National Survey on Drug Use and Health to assess past-month use of cigarettes, cigars, and blunts among a total of 8695 pregnant women and 162 451 nonpregnant women aged 18 to 44 years. RESULTS: Cigarette use was more prevalent than cigar or blunt use in pregnant and nonpregnant women, with higher prevalence in nonpregnant women for each product. Among all women, cigarette use decreased and blunt use increased over time, whereas cigar use remained stable. Smoking prevalence was highest in the first trimester. CONCLUSIONS: The health implications of the increase in blunt use are not well known in the scientific literature or by the general public. Given the rapid changes in state marijuana laws, this issue should be a public health priority.

Trends in and Characteristics of Marijuana and Menthol Cigarette Use Among Current Cigarette Smokers, 2005-2014.

Background: Given increasing co-marijuana and tobacco use in the United States, this study aimed to explore the overlap between menthol cigarette use (MCU) and marijuana. Methods: Data came from past month US cigarette smokers 12 years and older responding to the National Survey on Drug Use and Health between 2005 and 2014 (N = 51 500). Prevalence, demographics and substance use characteristics from 2013 to 2014 were assessed across four groups, based on past month marijuana and tobacco use: cigarette smokers with marijuana and MCU, with marijuana but no MCU, with no marijuana but MCU, and with use of neither. Multivariable logistic regression explored the relationship between MCU, marijuana, and dependence. Linear and quadratic trends were assessed using logistic regression with orthogonal polynomials. Results: Past month marijuana/MCU among cigarette smokers was 8.3% in 2013-2014. Overall, marijuana/MCU was significantly higher among blacks versus whites (20.8% vs. 5.8%, p < .0001), though among 12-25 year olds, prevalence was significantly higher among whites versus blacks (6.3% vs. 0.9% for 12-17-year-olds; 39.2% vs. 26.8% for 18-25-year-olds). Marijuana/MCU increased significantly between 2005 and 2014 overall, and among whites and blacks. No adjusted associations were found between marijuana, MCU and nicotine or marijuana dependence. Conclusions: Past month marijuana/MCU among cigarette smokers is increasing in the United States, with specific racial and age-based disparities. Research about the implications of consuming both marijuana and menthol, and the potential overlap in consumption of flavors across the products is warranted to better inform future preventive and treatment approaches. Implications: This is the first study to assess the overlap between MCU and marijuana use among a nationally representative sample of US current smokers ages 12 and older. Findings from this study suggest that past month marijuana and menthol use among cigarette smokers is increasing in the United States, with specific racial/ethnic and age-based disparities. More research about the implications of consuming both marijuana and menthol, and the potential overlap in consumption of flavors in marijuana and tobacco products is warranted to better understand what preventive and treatment approaches may be needed.

Sweet flowers are slow, and weeds make haste: leveraging methodology from research on tobacco, alcohol, and opioid analgesics to make rapid and policy-relevant advances in cannabis science.

The legalization of medical and recreational cannabis use has occurred ahead of science. The current evidence base has poor utility for determining if cannabis products can meet the standards of safety, efficacy, and quality intrinsic to modern medicine, and for informing regulation of cannabis as a legal intoxicant. Individual jurisdictions that pass cannabis reforms may not have adequate resources to support the level of new scientific research needed to inform regulatory actions; this could make it difficult to keep a rapidly growing multi-billion-dollar cannabis industry in check. Further, the present lack of evidence-based regulatory oversight for cannabis parallels the climates that gave rise to the tobacco and prescription opioid epidemics, suggesting that continued omission may result in negative public health consequences. However, translating a methodological framework developed through research on these compounds may promote rapid advances in cannabis science germane to regulatory knowledge gaps. The present review highlights specific advancements in these areas, as well as in alcohol regulation, that are prime for informing policy-relevant cannabis science, and also offers some recommendations for evidence-based regulatory policy. Resulting progress may directly inform both regulation of cannabis in both medical and licit recreational drug frameworks, and new cannabis-related public health initiatives.

Day-to-Day Variability in Self-Reported Cigarettes Per Day.

BACKGROUND AND AIMS: Nicotine addiction theory predicts small day-to-day variability in cigarettes/day (CPD) whereas social learning theory predicts large variability. A description of the variability in CPD over multiple days is not available. METHODS: We conducted secondary analyses of two natural history studies with daily smokers-one of smokers not intending to quit, and one of smokers intending to quit sometime in the next 3 months. In the former, smokers recorded their smoking during the day by Ecological Momentary Assessment, using a palm-top computer. In the latter, participants reported CPD nightly via a phone Interactive Voice Response system. Analyses were based on smokers who reported averaging ≥10 CPD, and on days in which there was no attempt to stop or reduce smoking. RESULTS: Across the two studies, on average, smokers had small changes in day-to-day CPD (mean changes were 2.2 and 2.9 CPD). However a minority averaged changing by ≥5 CPD from one day to the next (7% and 11%), and many changed by ≥5 CPD on at least 10 of the 90 days (8% and 31%). Neither smoking restrictions, dependence, stereotypy ratings, nor interest in quitting predicted variability. CONCLUSION: Although on average, smokers have little change day-to-day CPD, a substantial minority of smokers often change by 5 CPD from day-to-day. We did not find potential causes of this variability. IMPLICATIONS: Across day variability in CPD is larger than implied in prior studies. Determining causes of day-to-day variability should increase our understanding of the determinants of smoking.

Relationship of gambling with tobacco, alcohol, and illicit drug use among adolescents in the USA: Review of the literature 2000-2014.

BACKGROUND AND OBJECTIVES: Adolescence is a time during which not only gambling, but also tobacco, alcohol, and illicit drug use, usually begin. The purpose of this paper is to provide an updated review of the literature on gambling and its associations with tobacco, alcohol, and illicit drug use among US youth. METHODS: An electronic literature search of PubMed and PsycInfo was conducted for studies since 2000 using the keywords "smoking," "tobacco," "nicotine," "cigarette," "gambling," "adolescence," "adolescent," "alcohol," and "substance use." Ten articles with unique adolescent samples were located. Because the articles varied in regard to definitions of gambling, tobacco, alcohol, and drug use, we provide a qualitative review of included studies. RESULTS: Gambling prevalence rates ranged from 44.3% to 68% in national telephone-based surveys, from 24.4% to 86% among students in school-based surveys, and from 22.5% to 47.4% in surveys of convenience samples. Significant associations were reported between gambling and tobacco use (4/7 articles), gambling and alcohol use (7/8 articles), and gambling and illicit drug use (7/8 articles). CONCLUSIONS: The wide range in rates of gambling and problem gambling may be due in part to differences among the studies in participant samples, sampling techniques, assessment time frames, and definitions of gambling. Despite methodological differences, most studies showed significant associations of gambling with tobacco, alcohol, and other illicit drug use. SCIENTIFIC SIGNIFICANCE: As accessibility to gambling increases, more research is needed to inform prevention efforts and identify youth at-risk for gambling and other high-risk behaviors.

Electronic cigarettes in adults in outpatient substance use treatment: Awareness, perceptions, use, and reasons for use.

BACKGROUND AND OBJECTIVES: Most studies on e-cigarettes have come from population-based surveys. The current research aimed to provide initial data on e-cigarette awareness, perceptions, use, and reasons for use among adults seeking substance use treatment. METHODS: A survey was conducted among 198 participants ≥18 years old in a community-based outpatient substance use treatment program. RESULTS: Of the 198 participants, 69% currently smoked cigarettes, 92% were aware of e-cigarettes, and 58% had ever used e-cigarettes. The proportion of the number of participants who had ever used e-cigarettes to the number who currently smoked (89.7%) appeared higher than the corresponding proportion in the 2012-13 National Adult Tobacco Survey (78.3%). Almost half of the sample who reported ever using e-cigarettes endorsed quitting or reducing smoking as a reason for use, and 32% endorsed reasons for use relating to curiosity/experimentation. A greater likelihood of e-cigarette ever-use was significantly associated with younger age (adjusted odds ratio [AOR] = 0.94, 95%confidence interval [CI] = 0.90, 0.98) and perceptions related to using e-cigarettes in public places where smoking cigarettes is not allowed (AOR = 2.96, 95%CI = 1.18, 7.42) but was not associated with primary drug of choice. DISCUSSION AND CONCLUSIONS: E-cigarette use in adults seeking substance use treatment appears higher than it is in the US general population of smokers. The high frequency of use may be due to curiosity/experimentation or attempts to quit or reduce smoking. SCIENTIFIC SIGNIFICANCE: Future research may consider how e-cigarettes interact with other substance use and affect high rates of nicotine and tobacco use in this population.

Examination of the effects of cannabidiol on menstrual-related symptoms.

Some individuals attempt to alleviate menstrual-related symptoms (MRS) by using cannabis and report having expectations that cannabis can improve MRS; however, no study has examined the effect of cannabinoids on MRS. The present study is a pre-post, randomized, open-label trial that aimed to examine the effects of oral cannabidiol (CBD) isolate for alleviating MRS. Participants were assigned randomly to one of two open-label dosing groups of CBD softgels (160 mg twice a day, BID, n = 17; 320 mg BID, n = 16) and completed a 1-month baseline period. Following baseline, participants were instructed to consume CBD starting the first day they believed they experienced symptoms each month and to take their assigned dose daily for 5 consecutive days for three CBD-consumption months. We examined differences in MRS and related outcomes between baseline and 3 months of CBD consumption. Results revealed reductions (in both dosing groups) in MRS, irritability, anxiety, global impression of change, stress, and subjective severity scores when comparing baseline to all 3 months of CBD consumption. Depression scores did not change in either dosing group. Findings suggest that CBD may have the potential for managing MRS. Importantly, changes in symptoms appeared in the first month of CBD consumption and persisted over the 3 consumption months. Further research is warranted comparing the effects of CBD to placebo (a limitation of the study) and examining the potential to optimize CBD consumption for reducing MRS (e.g., combining CBD with terpenes; varying routes and timing of administration). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

LC-MS/MS quantification of Δ8-THC, Δ9-THC, THCV ISOMERS and their main metabolites in human plasma.

BACKGROUND: In recent years, potential therapeutic applications of several different cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC), its isomer Δ8-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV), have been investigated. Nevertheless, to establish dose-effect relationship and to gain knowledge of their pharmacokinetics and metabolism, sensitive and specific analytical assays are needed to measure these compounds in patients. For this reason, we developed and validated an online extraction high-performance liquid chromatography- tandem mass spectrometry (LC/LC-MS/MS) method for the simultaneous quantification of 13 cannabinoids and metabolites including the Δ8 and Δ9 isomers of THC, THCV and those of their major metabolites in human plasma. METHODS: Plasma was fortified with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL were extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization (APCI)-MS/MS running in the positive multiple reaction monitoring (MRM) mode. RESULTS: The lower limit of quantification ranged from 0.5 to 2.5 ng/mL and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 82.9 to 109% and 4.3 to 20.3% (coefficient of variance), respectively. Of 534 plasma samples following controlled oral administration of Δ8-THCV, 236 were positive for Δ8-THCV (median; interquartile ranges: 3.5 ng/mL; 1.8 - 11.9 ng/mL), 383 for the major metabolite (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabivarin (Δ8-THCV-COOH) (95.4 ng/mL; 20.7 - 328 ng/mL), 260 for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (Δ9-THCV-COOH) (5.8 ng/mL; 2.5 - 16.1 ng/mL), 157 for (-)-11-hydroxy-Δ8-tetrahydrocannabivarin (11-OH-Δ8-THCV) (1.7 ng/mL; 1.0 - 3.7 ng/mL), 49 for Δ8-THC-COOH (1.7 ng/mL; 1.4 - 2.3 ng/mL) and 42 for Δ9-THCV (1.3 ng/mL; 0.8 - 1.6 ng/mL). CONCLUSIONS: We developed and validated the first LC/LC-MS/MS assay for the specific quantification of Δ8-THC, Δ9-THC and THCV isomers and their respective metabolites in human plasma. Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH were the major Δ8-THCV metabolites in human plasma after oral administration of 98.6% pure Δ8-THCV.

Sex Differences in the Safety and Subjective Effects of Two Oral Δ9-Tetrahydrocannabinol-Containing Cannabis Products over Multiple Doses Among Healthy Adults.

Introduction: A growing number of females report consuming cannabis products. There is a paucity of data on sex differences in safety and subjective effects after repeated use of varying oral doses of Δ9-tetrahydrocannabinol (THC; the primary psychoactive constituent of cannabis). Materials and Methods: Data were from two randomized, double-blind, placebo-controlled, multiple-dose, between-subject trials of two THC-containing oral cannabis products. Healthy adults received placebo, low-dose THC (∼2.5 or ∼5 mg per dose), or high-dose THC (∼7.5 or ∼10 mg per dose) twice daily for 7 days. There were 38 males (8 placebo, 17 low-dose THC, 13 high-dose THC) and 46 females (8 placebo, 17 low-dose THC, 21 high-dose THC). Analyses compared adverse events (AEs) and subjective effects between males and females, by THC dose. Results: In the placebo and low-dose THC groups, there were no sex differences in the relative rate of AEs. In the high-dose THC group, females versus males reported 3.08 (95% confidence interval [CI]=1.31-8.33) times as many AEs. There were no significant interactions of sex×low-dose THC group for any subjective effect. In the high-dose THC group, females versus males reported greater "relaxed" ratings (b=15.14, 95% CI=1.44-28.84, p=0.027), whereas in the placebo group, males versus females reported greater ratings of "liking the effect" (b=-30.01, 95% CI=2.77-57.26, p=0.028). Although analyses were underpowered to assess the sex×THC dose×day interaction, the initial sex disparity in AEs and some subjective effects in the high-dose THC group appeared to shrink after the first day. Conclusions: In this exploratory analysis, sex differences in some responses to oral THC were nuanced. Females appeared more sensitive than males to AEs and some subjective effects at higher but not lower doses. Males reported higher ratings than females on some subjective effects in response to placebo. Initial sex differences in response to higher doses of oral THC tended to diminish over 7 days of dosing. If replicated, findings could help inform sex-specific dosing strategies of medical cannabis products and could help educate medical cannabis patients on any temporality of effects.

Effect of very low nicotine content cigarettes on alcohol drinking and smoking among adult smokers who are at-risk alcohol drinkers.

Alcohol and tobacco use are interrelated. This study examined response to very low nicotine content (VLNC) and moderate nicotine content (MNC) cigarettes by problematic drinking. We utilized a double-blind, randomized, within-subjects crossover design of VLNC and MNC cigarettes in two groups of adult cigarette smokers: with at-risk drinking (ARD; n = 23) and without ARD (n = 24). Participants smoked only their assigned experimental cigarette in their home environment for 7 days, and completed laboratory visits, including ad libitum smoking of the assigned experimental cigarette, at the beginning and end of each experimental week. Participants smoked their usual cigarettes for 7 days between conditions. Participants provided daily reports of alcohol and cigarette consumption. Current Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) alcohol use disorder (AUD) was assessed at baseline and the end of each experimental week. Compliance with smoking of experimental cigarettes was good. Adjusting for baseline drinking, there was no significant effect of experimental cigarette or ARD group on drinks per day or alcohol urges. There was no effect of experimental cigarette or ARD group on cigarettes per day, or on any puff topography outcome or postsmoking exhaled carbon monoxide during laboratory smoking. No participant had a change in AUD status or AUD severity. After 7 days of exposure to VLNC cigarettes, adult cigarette smokers with ARD did not show compensatory drinking or compensatory smoking behavior. A future policy change in the United States to reduce nicotine content in cigarettes may not produce unintended compensatory drinking or smoking among this vulnerable and prevalent population of smokers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).