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3.
BMC Psychiatry ; 24(1): 201, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38475757

ABSTRACT

BACKGROUND: Menthol cigarette use remains a large public health problem and disproportionately affects Black adults in the United States. The Food and Drug Administration has proposed prohibiting menthol flavor in cigarettes to protect public health. However, e-cigarettes are available in menthol flavor and are a popular alternative product adults might switch to if menthol is prohibited in cigarettes. Research is needed to understand how availability of menthol (vs. tobacco) flavored e-cigarettes could impact cigarette use among adults who smoke menthol cigarettes. METHODS: We will recruit 150 adults who currently smoke menthol cigarettes and will randomize them to 1 of 3 conditions modeling different regulatory scenarios. We will recruit equal numbers of participants identifying as Black vs. non-Black and will stratify randomization by race. To promote standardization and adherence, cigarette and e-cigarette products will be provided for 8 weeks based on the assigned condition: (A) no menthol restriction (menthol cigarette and menthol flavored e-cigarette), (B) menthol prohibited in cigarettes only (non-menthol cigarette and menthol flavored e-cigarette), (C) menthol prohibited in both cigarettes and e-cigarettes (non-menthol cigarette and tobacco flavored e-cigarette). A follow-up visit will occur at week 12 to assess tobacco use status. The study aims are to (1) examine the impact of prohibiting menthol flavor in cigarettes and e-cigarettes on smoking behavior and (2) investigate whether outcomes differ by race to understand the impact of menthol policies on Black (vs. non-Black) individuals given high rates of menthol cigarette use in this population. The primary outcome will evaluate changes in the number of cigarettes smoked per day during the 8-week study period and will examine differences by regulatory scenario. Secondary outcomes will compare percent days smoke-free, changes in nicotine dependence, and motivation, confidence, and intentions to quit smoking by the regulatory scenarios. We will examine whether changes in the outcomes differ by Black vs. non-Black participants to compare the magnitude of the effect of the various menthol policy scenarios by race. DISCUSSION: Results will contribute critical information regarding menthol in cigarettes and e-cigarettes to inform regulatory policies that maximize reductions in cigarette smoking and reduce tobacco-related health disparities. TRIAL REGISTRATION: NCT05259566. Yale IRB protocol #2000032211, last approved 12/8/2023.


Subject(s)
Cigarette Smoking , Electronic Nicotine Delivery Systems , Tobacco Products , Adult , Humans , United States , Menthol , Cigarette Smoking/epidemiology , Flavoring Agents , Tobacco Control , Randomized Controlled Trials as Topic
4.
PLoS One ; 18(9): e0291786, 2023.
Article in English | MEDLINE | ID: mdl-37733666

ABSTRACT

INTRODUCTION: Electronic cigarette (EC) use has increased rapidly in the last decade, especially among youth. Regulating nicotine delivery from ECs could help curb youth uptake and leverage EC use in harm reduction yet is complicated by varying device and liquid variables that affect nicotine delivery. Nicotine flux, the nicotine emission rate, is a parameter that incorporates these variables and focuses on the performance rather than the design of an EC. Nicotine flux therefore could be a powerful regulatory tool if it is shown empirically to predict nicotine delivery and subjective effects related to dependence. METHODS AND ANALYSIS: This project consists of two complementary clinical trials. In Trial I, we will examine the relationship between nicotine flux and the rate and dose of nicotine delivery from ECs, hence, impacting abuse liability. It will also examine the extent to which this relationship is mediated by nicotine form (i.e., freebase versus protonated). At Yale School of Medicine (YSM), study participants will puff EC devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. In Trial II, we will assess the relationship between nicotine flux, form, and subjective effects. At the American University of Beirut (AUB), participants will use EC devices with varying nicotine fluxes and forms, while dependency measures, such as the urge to use ECs, nicotine craving, and withdrawal symptoms, will be assessed. We will also monitor puffing intensity and real-time exposure to toxicants. ETHICS AND DISSEMINATION: The protocol of Trial I and Trial II was approved by YSM and AUB IRBs, respectively. We will disseminate study results through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: NCT05706701 for Trial I and NCT05430334 for Trial II.


Subject(s)
Electronic Nicotine Delivery Systems , Nicotine , Adolescent , Humans , Biological Transport , Craving , Cross-Over Studies
5.
Sci Rep ; 13(1): 11075, 2023 07 08.
Article in English | MEDLINE | ID: mdl-37422586

ABSTRACT

Dog ownership has been associated with reduced cardiovascular and all-cause mortality in civilian epidemiological samples. Associations between dog ownership and cardiometabolic disease were examined in the 2019-2020 wave of the National Health and Resilience in Veterans Study. Dog and cat ownership data were obtained from 3078 Veterans and cross-tabulated with self-reported, professionally diagnosed, heart disease, heart attack, stroke, high blood pressure, diabetes, and high cholesterol. In unadjusted tests, dog ownership was associated with lower rates of heart disease, high blood pressure, diabetes, and high cholesterol, while cat ownership was not. Relative to non-owners, dog owners were younger, were more likely to screen positive for posttraumatic stress disorder and/or major depressive disorder, and more active. Binary logistic regression models of associations between dog ownership and cardiometabolic disease were adjusted for age, sex, trauma load, mood disorder, substance abuse, nicotine abuse, and exercise. After adjustment, dog ownership was still associated with lower odds of hypertension and high cholesterol. Dog ownership also interacted with exercise to lower odds of heart disease and attenuated the effect of trauma load on hypertension. Conversely, age interacted with dog ownership such that odds of diabetes and stroke were higher in older Veterans who owned dogs.


Subject(s)
Cat Diseases , Depressive Disorder, Major , Diabetes Mellitus , Dog Diseases , Hypertension , Myocardial Infarction , Stroke , Veterans , Animals , Dogs , Cats , Humans , Pets , Hypertension/epidemiology , Cholesterol
6.
Sleep Breath ; 27(6): 2479-2490, 2023 12.
Article in English | MEDLINE | ID: mdl-37058215

ABSTRACT

BACKGROUND: Psychoactive substance use (i.e., nicotine, alcohol, and caffeine) has substantial effects on sleep architecture in healthy individuals, but their effects in those with obstructive sleep apnea (OSA) have not been well described. We aimed to describe the association between psychoactive substance use and sleep characteristics and daytime symptoms in individuals with untreated OSA. METHODS: We performed a secondary, cross-sectional analysis of The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Exposures included current smoking, alcohol and caffeine use in individuals with untreated OSA. Outcome domains included subjective and objective sleep characteristics, daytime symptoms, and comorbid conditions. Linear or logistic regression assessed the association between substance use and each domain (e.g., self-reported sleep duration, total polysomnographic sleep time, sleepiness, and anxiety). RESULTS: Of the 919 individuals with untreated OSA, 116 (12.6%) were current cigarette smokers, 585 (63.7%) were moderate or heavy alcohol users, and 769 (83.7%) were moderate or heavy caffeine users. Participants were on average 52.2±11.9 years old, 65.2% were male with a median BMI of 30.6 (IQR: 27.2, 35.9, kg/m2). Current smokers exhibited lower sleep duration (0.3 h), longer sleep latency (5 min) compared with non-smokers (all p-values < 0.05). People with heavy or moderate alcohol use exhibited more REM sleep (2.5 and 5% of total sleep time respectively), as did those with moderate caffeine use (2%, p-values < 0.05). The combined smoker plus caffeine group exhibited shorter sleep duration (0.4 h, p-value < 0.05) and higher risk for chronic pain [Odds Ratio (95%CI) = 4.83 (1.57, 14.9) compared with non-users. CONCLUSIONS: Psychoactive substance use is associated with sleep characteristics and clinically relevant correlates in people with untreated OSA. Further investigation into the effects that various substances have on this population may present opportunities to understand disease mechanisms more fully and increase the effectiveness of treatment in OSA.


Subject(s)
Sleep Apnea, Obstructive , Substance-Related Disorders , Humans , Male , Adult , Middle Aged , Female , Caffeine/adverse effects , Nicotine , Cross-Sectional Studies , Ethanol
7.
Int Rev Neurobiol ; 168: 265-310, 2023.
Article in English | MEDLINE | ID: mdl-36868631

ABSTRACT

The role of glutamate system in the etiology and pathophysiology of psychiatric disorders has gained considerable attention in the past two decades, including dysregulation of the metabotropic glutamatergic receptor subtype 5 (mGlu5). Thus, mGlu5 may represent a promising therapeutic target for psychiatric conditions, particularly stress-related disorders. Here, we describe mGlu5 findings in mood disorders, anxiety, and trauma disorders, as well as substance use (specifically nicotine, cannabis, and alcohol use). We highlight insights gained from positron emission tomography (PET) studies, where possible, and discuss findings from treatment trials, when available, to explore the role of mGlu5 in these psychiatric disorders. Through the research evidence reviewed in this chapter, we make the argument that, not only is dysregulation of mGlu5 evident in numerous psychiatric disorders, potentially functioning as a disease "biomarker," the normalization of glutamate neurotransmission via changes in mGlu5 expression and/or modulation of mGlu5 signaling may be a needed component in treating some psychiatric disorders or symptoms. Finally, we hope to demonstrate the utility of PET as an important tool for investigating mGlu5 in disease mechanisms and treatment response.


Subject(s)
Mental Disorders , Receptor, Metabotropic Glutamate 5 , Humans , Mood Disorders , Biomarkers , Glutamates
8.
Open Forum Infect Dis ; 10(3): ofad089, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36968969

ABSTRACT

Background: Nicotine replacement therapy, bupropion, and varenicline are smoking cessation medications (SCMs) shown to be similarly effective in people with and without human immunodeficiency virus (PWH and PWoH, respectively), although rates of receipt of these medications are unknown. Methods: We identified patients in the Veterans Aging Cohort Study with electronic health record-documented current smoking using clinical reminder data for tobacco use (2003-2018). We measured receipt of SCMs using Veterans Affairs pharmacy data for outpatient prescriptions filled 0-365 days after current smoking documentation. We used log-linear, Poisson-modified regression models to evaluate the relative risk (RR) for receiving SCM by human immunodeficiency virus (HIV) status, the annual rate of receipt, and rate difference among PWH relative to PWoH. Results: The sample included 92 632 patients (29 086 PWH), reflecting 381 637 documentations of current smoking. From 2003 to 2018, the proportion receiving SCMs increased from 15% to 34% for PWH and from 17% to 32% among PWoH. There was no statistical difference in likelihood of receiving SCM by HIV status (RR, 1.010; 95% confidence interval [CI], .994-1.026). Annual rates of receiving SCM increased for PWH by 4.3% per year (RR, 1.043; 95% CI, 1.040-1.047) and for PWoH by 3.7% per year (RR, 1.037; 95% CI, 1.036-1.038; rate difference +0.6% [RR, 1.006; 95% CI, 1.004-1.009]). Conclusions: In a national sample of current smokers, receipt of SCM doubled over the 16-year period, and differences by HIV status were modest. However, fewer than 35% of current smokers receive SCM annually. Efforts to improve SCM receipt should continue for both groups given the known dangers of smoking.

9.
Ann Am Thorac Soc ; 20(8): 1182-1191, 2023 08.
Article in English | MEDLINE | ID: mdl-36917194

ABSTRACT

Rationale: Poor adherence limits the effectiveness of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). A better understanding of CPAP adherence is needed to develop novel strategies to improve it. Objectives: To determine if the chronotype (morning, evening, or intermediate) of patients with OSA is associated with differences in CPAP adherence. If such an association exists, determine the mechanisms underlying this association. Methods: We performed a secondary analysis of the APPLES (Apnea Positive Pressure Long-term Efficacy Study) clinical trial. We assessed chronotype using the Morningness-Eveningness Questionnaire (MEQ) among participants randomized to the CPAP arm with daily adherence data (n = 469). Evening (MEQ ⩽ 41), intermediate (41 < MEQ < 59), and morning type (MEQ ⩾ 59) categories were the exposures. We modeled daily CPAP use (hours per night) over a 6-month period, using a linear mixed model, adjusted for covariates (e.g., age, sex, marital status). To assess mechanisms of the association, we performed mediation analyses using sleep duration, weekend catch-up sleep, depression, and other factors. Results: Most participants were obese men with severe OSA (body mass index of 32.3 ± 7.3 kg/m2, 65% male, and apnea-hypopnea index 39.8 ± 24.6/h). Participants were 44% morning, 47% intermediate, and 8% evening chronotype. Participants with the morning chronotype reported the shortest sleep duration on weekends (7.3 vs. 7.6 and 7.9 h/night) compared with the intermediate and evening types. Participants with the morning chronotype exhibited a 40-min/night higher CPAP use (P = 0.001) than persons with the intermediate chronotype. This relationship was mildly attenuated (32.8 min/night; P = 0.011) after adjustment for covariates. None of the selected factors (e.g., sleep duration, weekend catch-up sleep) exhibited a significant mediation effect. Conclusions: Morning chronotype is associated with a clinically meaningful increase in CPAP adherence compared with other chronotypes. Mechanisms of this association require further study. Chronotype may be a novel predictor of CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT00051363).


Subject(s)
Chronotype , Sleep Apnea, Obstructive , Humans , Male , Female , Continuous Positive Airway Pressure , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/complications , Sleep , Body Mass Index , Patient Compliance
10.
Chronic Stress (Thousand Oaks) ; 7: 24705470231154842, 2023.
Article in English | MEDLINE | ID: mdl-36843572

ABSTRACT

Metabotropic glutamate receptor 5 (mGluR5) dysregulation has been implicated in the pathophysiology of many psychiatric disorders, as well as nicotine use and dependence. We used positron emission tomography with [18F]FPEB to measure mGluR5 availability in vivo in 6 groups: (1) nicotine users (NUs) without other psychiatric comorbidities (n = 23); (2) comparison controls (CCs) without nicotine use or psychiatric comorbidities (n = 38); (3) major depressive disorder subjects with concurrent nicotine use (MDD-NU; n = 19); (4) MDD subjects without concurrent nicotine use (MDD-CC; n = 20); (5) posttraumatic stress disorder subjects with concurrent nicotine use (PTSD-NU; n = 17); and (6) PTSD subjects without concurrent nicotine use (PTSD-CC; n = 16). The goal of the study was to test the hypothesis that mGluR5 availability in key corticolimbic regions of interest (ROIs) is different in NU with versus without comorbid psychiatric disorders (ROI: dorsolateral prefrontal cortex [dlPFC], orbitofrontal cortex [OFC], ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC], amygdala, hippocampus). We found that NU had 11%-13% lower mGluR5 availability in OFC, vmPFC, dlPFC, and ACC as compared with CC, while PTSD-NU had 9%-11% higher mGluR5 availability in OFC, dlPFC, and ACC compared with PTSD. Furthermore, relationships between mGluR5 availability and psychiatric symptoms varied as a function of psychiatric diagnosis among NUs. NU showed a negative correlation between mGluR5 and smoking cravings and urges (r's = -0.58 to -0.70, p's = 0.011 - 0.047), while PTSD-NU had the reverse relationship (r's = 0.60-0.71, p's = 0.013-0.035 in ACC, vmPFC, and dlPFC). These findings have substantial implications for our understanding of glutamate homeostasis in psychiatric subgroups and for identifying key neural phenotypes among NU. mGluR5 is a potential treatment target for precision medicine in individuals with nicotine use.

11.
Neuropsychopharmacology ; 48(4): 683-689, 2023 03.
Article in English | MEDLINE | ID: mdl-36681758

ABSTRACT

The cholinergic system is a critical mediator of cognition in animals. People who smoke cigarettes exhibit cognitive deficits, especially during quit attempts. Few studies jointly examine the cholinergic system and cognition in people while trying to quit smoking. We used positron emission tomography (PET) brain imaging with the ß2-subunit containing nicotinic acetylcholine receptor (ß2*-nAChR) partial agonist radioligand (-)-[18F]flubatine and the acetylcholinesterase inhibitor physostigmine to jointly examine the cholinergic system, smoking status, and cognition. (-)-[18F]Flubatine scans and cognitive data were acquired from twenty people who recently stopped smoking cigarettes (aged 38 ± 11 years; 6 female, 14 male; abstinent 7 ± 1 days) and 27 people who never smoked cigarettes (aged 29 ± 8 years; 11 female, 16 male). A subset of fifteen recently abstinent smokers and 21 never smokers received a mid-scan physostigmine challenge to increase acetylcholine levels. Regional volume of distribution (VT) was estimated with equilibrium analysis at "baseline" and post-physostigmine. Participants completed a cognitive battery prior to (-)-[18F]flubatine injection and physostigmine administration assessing executive function (Groton Maze Learning test), verbal learning (International Shopping List test), and working memory (One Back test). Physostigmine significantly decreased cortical (-)-[18F]flubatine VT, consistent with increased cortical acetylcholine levels reducing the number of ß2*-nAChR sites available for (-)-[18F]flubatine binding, at comparable magnitudes across groups (p values < 0.05). A larger magnitude of physostigmine-induced decrease in (-)-[18F]flubatine VT was significantly associated with worse executive function in people who recently stopped smoking (p values < 0.05). These findings underscore the role of the cholinergic system in early smoking cessation and highlight the importance of neuroscience-informed treatment strategies.


Subject(s)
Acetylcholine , Receptors, Nicotinic , Animals , Male , Female , Acetylcholine/metabolism , Acetylcholinesterase , Physostigmine , Positron-Emission Tomography/methods , Brain/diagnostic imaging , Brain/metabolism , Receptors, Nicotinic/metabolism , Cognition , Cholinergic Agents , Smoking/adverse effects
12.
Nicotine Tob Res ; 24(5): 745-752, 2022 03 26.
Article in English | MEDLINE | ID: mdl-34628508

ABSTRACT

INTRODUCTION: Chronic nicotine exposure desensitizes dopamine responses in animals, but it is not known if this occurs in human tobacco smokers. Deficits in dopamine function are likely to make smoking cessation difficult. We used positron emission tomography (PET) brain imaging with the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO to determine if abstinent smokers exhibit less amphetamine-induced dopamine release in the ventral striatum than nonsmokers, and whether this was associated with clinical correlates of smoking cessation. METHODS: Baseline [11C]-(+)-PHNO scans were acquired from smokers (n = 22, 7 female, abstinent 11 ± 9 days) and nonsmokers (n = 20, 7 female). A subset of thirty-seven participants (18 smokers) received oral amphetamine (0.5 mg/kg) three hours before a second [11C]-(+)-PHNO scan. Binding potential (BPND) (i.e., D2/3 receptor availability) was estimated at baseline and postamphetamine in the ventral striatum. Amphetamine-induced percent change in BPND was calculated to reflect dopamine release. Subjects also completed the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: There were no group differences in baseline BPND. Amphetamine-induced percent change in BPND in the ventral striatum was significantly lower in abstinent smokers compared to nonsmokers (p=0.019; d=0.82). Higher CES-D scores were significantly associated with lower ventral striatal percent change in BPND for abstinent smokers (rs=-0.627, p=0.025). CONCLUSIONS: In conclusion, abstinent smokers exhibited significantly less amphetamine-induced dopamine release in the ventral striatum than nonsmokers. In abstinent smokers, worse mood was significantly associated with less striatal dopamine release. Our findings highlight a potential neural mechanism that may underlie negative mood symptoms during early abstinence. IMPLICATIONS: This study combined quantitative PET imaging and an amphetamine challenge to examine striatal dopamine function during early smoking cessation attempts. The findings demonstrate that recently abstinent tobacco smokers exhibit significant, mood-associated striatal dopamine dysfunction compared to nonsmokers. This study advances our knowledge of the neurobiology underlying early quit attempts, and bridges novel neural findings with clinically relevant symptoms of smoking cessation. These results may explain the challenge of maintaining long-term abstinence from smoking, and can lend insight into the development of treatment strategies for smoking cessation.


Subject(s)
Dopamine , Ventral Striatum , Animals , Carbon Radioisotopes , Dopamine/metabolism , Female , Humans , Non-Smokers , Positron-Emission Tomography/methods , Smokers , Ventral Striatum/diagnostic imaging , Ventral Striatum/metabolism
13.
Neuropsychopharmacology ; 47(2): 543-552, 2022 01.
Article in English | MEDLINE | ID: mdl-34294874

ABSTRACT

Obesity is a serious medical condition that often co-occurs with stress-related psychiatric disorders. It is recognized that the brain plays a key role in the (patho)physiology of obesity and that there is a bidirectional relationship between obesity and psychopathology, yet molecular mechanisms altered in obesity have not been fully elucidated. Thus, we investigated relationships between obesity and synaptic density in vivo using the radioligand [11C]UCB-J (which binds to synaptic glycoprotein SV2A) and positron emission tomography in individuals with obesity, and with or without stress-related psychiatric disorders. Regions of interest were the dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial, amygdala, hippocampus, and cerebellum. Forty individuals with a body mass index (BMI) ≥ 25 kg/m2 (overweight/obese), with (n = 28) or without (n = 12) psychiatric diagnosis, were compared to 30 age- and sex-matched normal weight individuals (BMI < 25), with (n = 14) or without (n = 16) psychiatric diagnosis. Overall, significantly lower synaptic density was observed in overweight/obese relative to normal weight participants (ηp2 = 0.193, F = 2.35, p = 0.042). Importantly, in participants with stress-related psychiatric diagnoses, we found BMI to be negatively correlated with synaptic density in all regions of interest (p ≤ 0.03), but no such relationship observed for mentally healthy controls (p ≥ 0.68). In the stress-related psychiatric groups, dorsolateral prefrontal cortex synaptic density was negatively associated with measures of worry (r = -0.46, p = 0.01), tension/anxiety (r = -0.38, p = 0.04), fatigue (r = -0.44, p = 0.02), and attentional difficulties (r = -0.44, p = 0.02). In summary, the findings of this novel in vivo experiment suggest compounding effects of obesity and stress-related psychopathology on the brain and the associated symptomatology that may impact functioning. This offers a novel biological mechanism for the relationship between overweight/obesity and stress-related psychiatric disorders that may guide future intervention development efforts.


Subject(s)
Brain , Positron-Emission Tomography , Brain/metabolism , Cognition , Hippocampus , Humans , Obesity/diagnostic imaging , Positron-Emission Tomography/methods
14.
Prev Med Rep ; 23: 101444, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34235048

ABSTRACT

Given accumulating evidence that electronic nicotine delivery systems (ENDS) may be a harm-reduction alternative to combustible tobacco products, it is important to understand the real-world implications of these devices in the populations that may benefit from them the most. We surveyed the use, perceptions of, and interest in using ENDS among patients attending their initial low-dose CT scan (LDCT) for lung cancer screening (LCS) who reported current smoking, a cohort of older individuals at high-risk for lung cancer and other smoking-related illnesses due to their heavy smoking history (30 or more pack years). Participants (N = 107) completed the survey in clinic immediately before their shared decision-making visit for lung cancer screening on the day of their LDCT. Approximately a quarter of participants reported ever use of ENDS in the past; nearly a third expressed a willingness to try switching to them in the future. Prior ENDS use was significantly associated with willingness to try switching to ENDS in the future. The most common reasons to consider switching included smoking cessation and harm reduction. Only about a third were aware that ENDS are not approved by the FDA for smoking cessation; knowledge significantly varied by demographic and clinical characteristics. These findings have important implications for ENDS public health campaigns and tobacco harm reduction strategies for older individuals who smoke.

15.
Cereb Cortex ; 31(6): 2787-2798, 2021 05 10.
Article in English | MEDLINE | ID: mdl-33442731

ABSTRACT

Acetylcholine (ACh) has distinct functional roles in striatum compared with cortex, and imbalance between these systems may contribute to neuropsychiatric disease. Preclinical studies indicate markedly higher ACh concentrations in the striatum. The goal of this work was to leverage positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors to explore ACh variation across the human brain, because these measures can be influenced by competition with endogenous neurotransmitter. PET scans were analyzed from healthy human volunteers (n = 4) and nonhuman primates (n = 2) scanned with the M1-selective radiotracer [11C]LSN3172176 in the presence of muscarinic antagonist scopolamine, and human volunteers (n = 10) scanned with the α4ß2* nicotinic ligand (-)-[18F]flubatine during nicotine challenge. In all cases, occupancy estimates within striatal regions were consistently lower (M1/scopolamine human scans, 31 ± 3.4% occupancy in striatum, 43 ± 2.9% in extrastriatal regions, p = 0.0094; nonhuman primate scans, 42 ± 26% vs. 69 ± 28%, p < 0.0001; α4ß2*/nicotine scans, 67 ± 15% vs. 74 ± 16%, p = 0.0065), indicating higher striatal ACh concentration. Subject-level measures of these concentration differences were estimated, and whole-brain images of regional ACh concentration gradients were generated. These results constitute the first in vivo estimates of regional variation in ACh concentration in the living brain and offer a novel experimental method to assess potential ACh imbalances in clinical populations.


Subject(s)
Acetylcholine/metabolism , Brain/diagnostic imaging , Brain/metabolism , Positron-Emission Tomography/methods , Radiopharmaceuticals/metabolism , Adult , Animals , Brain/drug effects , Female , Humans , Indoles/metabolism , Indoles/pharmacology , Macaca mulatta , Male , Middle Aged , Piperidines/metabolism , Piperidines/pharmacology , Radiopharmaceuticals/pharmacology , Receptor, Muscarinic M1/agonists , Receptor, Muscarinic M1/metabolism , Receptors, Nicotinic/metabolism , Scopolamine/metabolism , Scopolamine/pharmacology , Young Adult
17.
Cancer Prev Res (Phila) ; 14(1): 5-10, 2021 01.
Article in English | MEDLINE | ID: mdl-33148678

ABSTRACT

Electronic nicotine delivery systems (ENDS; i.e., electronic cigarettes, e-cigarettes, vaping devices, vape pens) were introduced to the U.S. market in 2007 as a potential harm reduction alternative for people who smoked combustible cigarettes. Since that time, ENDS popularity grew very quickly, particularly among individuals who smoke cigarettes. However, young people and never smokers also started using ENDS, cohorts for whom these products were not intended. There are now a broad range of devices and e-liquid constituents. ENDS devices vary considerably in their design and generation of potentially toxic chemicals, with higher power devices likely much more hazardous than lower power devices. This landscape may further change after September 9, 2020, when all ENDS manufacturers are required to submit a premarket tobacco product application to the FDA to obtain authorization for marketing. Research has not kept pace with this rapidly changing technology and important questions remain regarding the relative benefits versus risks of ENDS. In light of these challenges, we propose key ENDS research priorities to address these gaps.


Subject(s)
Cigarette Smoking/therapy , Electronic Nicotine Delivery Systems , Smoking Cessation/methods , Vaping/adverse effects , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cigarette Smoking/adverse effects , Humans , Neoplasms/etiology , Neoplasms/prevention & control , Nicotine/administration & dosage , Nicotine/adverse effects , Respiratory Tract Diseases/etiology , Respiratory Tract Diseases/prevention & control , Vaping/legislation & jurisprudence
18.
Clin Chest Med ; 41(4): 797-807, 2020 12.
Article in English | MEDLINE | ID: mdl-33153696

ABSTRACT

Electronic cigarettes (EC) are battery-operated devices that heat and aerosolize a liquid solution that typically contains nicotine. ECs have become commonly used among youth and may pose substantial risks of future addiction and health problems in this population. However, ECs are far less toxic per puff compared with combustible cigarettes, and as a result, might present an important harm reduction opportunity for cigarette smokers who cannot stop smoking by traditional means. The long-term health effects of ECs on individuals and the net effect on public health will remain unknown for many years.


Subject(s)
Electronic Nicotine Delivery Systems , Tobacco Use Disorder/complications , Humans
19.
Addict Res Theory ; 28(2): 160-164, 2020.
Article in English | MEDLINE | ID: mdl-32952489

ABSTRACT

BACKGROUND: Veterans are a unique population that may be at increased risk of tobacco use disorder and nicotine dependence (ND). We analyzed data from the National Health and Resilience in Veterans Study (NHRVS), a large nationally representative sample of US veterans, in order to more fully understand the prevalence and correlates of lifetime ND in US Veterans. METHODS: Descriptive statistics were conducted to summarize health and functioning/quality of life characteristics among veterans with and without lifetime ND. Hierarchical binary logistic regression analyses were conducted to evaluate the relationship between ND and psychiatric and physical health variables. RESULTS: Compared with veterans without lifetime ND, veterans with lifetime ND were more likely to screen positive for several lifetime psychiatric disorders including current alcohol use disorder (odds ratio [OR] 2.79 [95% confidence interval [CI] 2.23, 3.49]), depression (OR 1.86 [1.38, 2.50]), and PTSD (OR 1.68 [1.14, 2.47]). From a medical standpoint, they were more likely to endorse having kidney disease (OR 4.18 [2.55, 6.86]), heart attack (OR 2.09 [1.51, 2.89]), and rheumatoid arthritis (1.90 [1.20, 3.00]) in addition to other conditions. They scored lower in overall physical functioning and higher in somatization symptoms. CONCLUSIONS: Veterans with lifetime ND in the NHRVS survey were more likely to have psychiatric and medical conditions and lower physical functioning compared with Veterans without lifetime ND. Veterans with lifetime ND may therefore require a comprehensive and integrated approach to care that includes attention to co-morbid illness in addition to drug addiction.

20.
Am J Prev Med ; 59(3): 449-454, 2020 09.
Article in English | MEDLINE | ID: mdl-32684361

ABSTRACT

INTRODUCTION: As of February 18, 2020, states have reported 2,807 cases of e-cigarette, or vaping, product use-associated lung injury to the Centers for Disease Control and Prevention. Most cases involved cannabinoids. This study identifies current risk factors for adult marijuana vaping by analyzing 2017 and 2018 Behavioral Risk Factor Surveillance System data. METHODS: Data on 8,255 people who recently used marijuana were analyzed in September 2019. Sample-weighted multivariate logistic regressions considered a binary indicator for vaping as the primary method of marijuana use. Adjusting for demographic controls, regressions assessed the association between marijuana vaping and marijuana use for medical purposes (versus nonmedical only), current conventional cigarette use, current nicotine e-cigarette use, and 2 mental health variables. Demographic controls were binary indicators for female sex, Hispanic ethnicity, race, and having completed ≥1 year of college. RESULTS: Odds of marijuana vaping were higher among those who reported using for medical purposes (AORage18-24years=3.8, 95% CI=1.91, 7.67; AORage25-54years=1.8, 95% CI=1.02, 3.08; AORage55-64years=2.3, 95% CI=0.75, 7.07) and lower among people who smoked combustible cigarettes (AORage18-24years=0.2, 95% CI=0.06, 0.65; AORage25-54years=0.2, 95% CI=0.10, 0.26; AORage55-64years=0.1, 95% CI=0.05, 0.34). Vaping nicotine e-cigarettes was associated with greater odds of vaping marijuana for adults aged 25-54 years (AOR=4.6, 95% CI=2.70, 7.78) but not those aged 18-24 years (AOR=0.9, 95% CI=0.33, 2.26). CONCLUSIONS: Among people who use marijuana, adults reporting medical marijuana use were more likely to vape as their primary mode of consumption, whereas conventional cigarette smokers were less likely to do so. Use of nicotine e-cigarettes was associated with a greater likelihood of vaping marijuana for adults aged 25-54 years.


Subject(s)
Cannabis , Electronic Nicotine Delivery Systems , Vaping , Adolescent , Adult , Behavioral Risk Factor Surveillance System , Female , Humans , Male , Middle Aged , Smokers , Young Adult
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