this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).Monkeypox, a zoonotic infection caused by an orthopoxvirus, is endemic in parts of Africa. On August 4, 2022, the U.S. Department of Health and Human Services declared the U.S. monkeypox outbreak, which began on May 17, to be a public health emergency (1,2). After detection of the first U.S. monkeypox case), CDC and health departments implemented enhanced monkeypox case detection and reporting. Among 2,891 cases reported in the United States through July 22 by 43 states, Puerto Rico, and the District of Columbia (DC), CDC received case report forms for 1,195 (41%) cases by July 27. Among these, 99% of cases were among men; among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before symptom onset. Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons. Forty-two percent of persons with monkeypox with available data did not report the typical prodrome as their first symptom, and 46% reported one or more genital lesions during their illness; 41% had HIV infection. Data suggest that widespread community transmission of monkeypox has disproportionately affected gay, bisexual, and other men who have sex with men and racial and ethnic minority groups. Compared with historical reports of monkeypox in areas with endemic disease, currently reported outbreak-associated cases are less likely to have a prodrome and more likely to have genital involvement. CDC and other federal, state, and local agencies have implemented response efforts to expand testing, treatment, and vaccination. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, while addressing equity, minimizing stigma, and maintaining vigilance for transmission in other populations. Clinicians should test patients with rash consistent with

BACKGROUND We measured Δ9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) disposition in oral fluid (OF) following controlled cannabis smoking to evaluate whether monitoring multiple cannabinoids in OF improved OF test interpretation. METHODS Cannabis smokers provided written informed consent for this institutional review board–approved study. OF was collected with the Quantisal™ device following ad libitum smoking of one 6.8% THC cigarette. Cannabinoids were quantified by 2-dimensional GC-MS. We evaluated 8 alternative cutoffs based on different drug testing program needs. RESULTS 10 participants provided 86 OF samples −0.5 h before and 0.25, 0.5, 1, 2, 3, 4, 6, and 22 h after initiation of smoking. Before smoking, OF samples of 4 and 9 participants were positive for THC and THCCOOH, respectively, but none were positive for CBD and CBN. Maximum THC, CBD, and CBN concentrations occurred within 0.5 h, with medians of 644, 30.4, and 49.0 μg/L, respectively. All samples were THC positive at 6 h (2.1–44.4 μg/L), and 4 of 6 were positive at 22 h. CBD and CBN were positive only up to 6 h in 3 (0.6–2.1 μg/L) and 4 (1.0–4.4 μg/L) participants, respectively. The median maximum THCCOOH OF concentration was 115 ng/L, with all samples positive to 6 h (14.8–263 ng/L) and 5 of 6 positive at 22 h. CONCLUSIONS By quantifying multiple cannabinoids and evaluating different analytical cutoffs after controlled cannabis smoking, we determined windows of drug detection, found suggested markers of recent smoking, and minimized the potential for passive contamination.

BACKGROUND There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. METHODS We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. RESULTS Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. CONCLUSIONS Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513

Background People living with HIV ( PLWH ) experience higher risk of myocardial infarction ( MI ) and heart failure ( HF ) compared with uninfected individuals. Risk of other cardiovascular diseases ( CVD s) in PLWH has received less attention. Methods and Results We studied 19 798 PLWH and 59 302 age‐ and sex‐matched uninfected individuals identified from the MarketScan Commercial and Medicare databases in the period 2009 to 2015. Incidence of CVD s, including MI , HF , atrial fibrillation, peripheral artery disease, stroke and any CVD ‐related hospitalization, were identified using validated algorithms. We used adjusted Cox models to estimate hazard ratios and 95% CI s of CVD end points and performed probabilistic bias analysis to control for unmeasured confounding by race. After a mean follow‐up of 20 months, patients experienced 154 MI s, 223 HF , 93 stroke, 397 atrial fibrillation, 98 peripheral artery disease, and 935 CVD hospitalizations (rates per 1000 person‐years: 1.2, 1.7, 0.7, 3.0, 0.8, and 7.1, respectively). Hazard ratios (95% CI ) comparing PLWH with uninfected controls were 1.3 (0.9–1.9) for MI , 3.2 (2.4–4.2) for HF , 2.7 (1.7–4.0) for stroke, 1.2 (1.0–1.5) for atrial fibrillation, 1.1 (0.7–1.7) for peripheral artery disease, and 1.7 (1.5–2.0) for any CVD hospitalization. Adjustment for unmeasured confounding led to similar associations (1.2 [0.8–1.8] for MI , 2.8 [2.0–3.8] for HF , 2.3 [1.5–3.6] for stroke, 1.3 [1.0–1.7] for atrial fibrillation, 0.9 [0.5–1.4] for peripheral artery disease, and 1.6 [1.3–1.9] for CVD hospitalization). Conclusions In a large health insurance database, PLWH have an elevated risk of CVD , particularly HF and stroke. With the aging of the HIV population, developing interventions for cardiovascular health promotion and CVD prevention is imperative.

Development and validation of a method for simultaneous identification and quantification of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), and metabolites 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) in oral fluid. Simultaneous analysis was problematic due to different physicochemical characteristics and concentration ranges. Neutral analytes, such as THC and CBD, are present in ng/mL, rather than pg/mL concentrations, as observed for the acidic THCCOOH biomarker in oral fluid. THCCOOH is not present in cannabis smoke, definitively differentiating cannabis use from passive smoke exposure. THC, 11-OH-THC, THCCOOH, CBD, and CBN quantification was achieved in a single oral fluid specimen collected with the Quantisal™ device. One mL oral fluid/buffer solution (0.25mL oral fluid and 0.75mL buffer) was applied to conditioned CEREX ® Polycrom™ THC solid phase extraction (SPE) columns. After washing, THC, 11-OH-THC, CBD, and CBN were eluted with hexane/acetone/ethyl acetate (60:30:20, v/v/v), derivatized with N, O-bis-(trimethylsilyl) trifluoroacetamide and quantified by two-dimensional gas chromatography electron ionization mass spectrometry (2D-GCMS) with cold trapping. Acidic THCCOOH was separately eluted with hexane/ethyl acetate/acetic acid (75:25:2.5, v/v/v), derivatized with trifluoroacetic anhydride and hexafluoroisopropanol, and quantified by the more sensitive 2D-GCMS-electron capture negative chemical ionization (NCI-MS). Linearity was 0.5-50ng/mL for THC, 11-OH-THC, CBD and 1-50ng/mL for CBN. The linear dynamic range for THCCOOH was 7.5-500pg/mL. Intra-and inter-assay imprecision as percent RSD at three concentrations across the linear dynamic range were 0.3%-6.6%. Analytical recovery was within 13.8% of target. This new SPE 2D-GCMS assay achieved efficient quantification of five cannabinoids in oral fluid, including pg/mL concentrations of THCCOOH by combining differential elution, 2D-GCMS with electron ionization and negative chemical ionization. This method will be applied to quantification of cannabinoids in oral fluid specimens from individuals participating in controlled cannabis and Sativex ® (50% THC and 50% CBD) administration studies, and during cannabis withdrawal.

Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.

Fifty-three head hair specimens were collected from 38 males with a history of cannabis use documented by questionnaire, urinalysis and controlled, double blind administration of delta9-tetrahydrocannabinol (THC) in an institutional review board approved protocol. The subjects completed a questionnaire indicating daily cannabis use (N=18) or non-daily use, i.e. one to five cannabis cigarettes per week (N=20). Drug use was also documented by a positive cannabinoid urinalysis, a hair specimen was collected from each subject and they were admitted to a closed research unit. Additional hair specimens were collected following smoking of two 2.7% THC cigarettes (N=13) or multiple oral doses totaling 116 mg THC (N=2). Cannabinoid concentrations in all hair specimens were determined by ELISA and GCMSMS. Pre- and post-dose detection rates did not differ statistically, therefore, all 53 specimens were considered as one group for further comparisons. Nineteen specimens (36%) had no detectable THC or 11-nor-9-carboxy-THC (THCCOOH) at the GCMSMS limits of quantification (LOQ) of 1.0 and 0.1 pg/mg hair, respectively. Two specimens (3.8%) had measurable THC only, 14 (26%) THCCOOH only, and 18 (34%) both cannabinoids. Detection rates were significantly different (p<0.05, Fishers' exact test) between daily cannabis users (85%) and non-daily users (52%). There was no difference in detection rates between African-American and Caucasian subjects (p>0.3, Fisher's exact test). For specimens with detectable cannabinoids, concentrations ranged from 3.4 to >100 pg THC/mg and 0.10 to 7.3 pg THCCOOH/mg hair. THC and THCCOOH concentrations were positively correlated (r=0.38, p<0.01, Pearson's product moment correlation). Using an immunoassay cutoff concentration of 5 pg THC equiv./mg hair, 83% of specimens that screened positive were confirmed by GCMSMS at a cutoff concentration of 0.1 pg THCCOOH/mg hair.

Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography-mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean+/-SE peak concentrations of 300.4+/-24.6 ng/mL (low) and 639.1+/-56.8 ng/mL (high) 30-40 min after dosing. BE and EME generally were first detected in plasma 5-15 min post-dose; 2-4 h after dosing, BE and EME reached mean maximum concentrations of 321.3+/-18.4 (low) and 614.7+/-46.0 ng/mL (high) and 47.4+/-3.0 (low) and 124.4+/-18.2 ng/mL (high), respectively. Times of last detection were BE>EME>cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations