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Journal of Cannabis Research May 2024Cannabis has been shown to impact driving due to changes produced by delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. Current legal thresholds...
BACKGROUND
Cannabis has been shown to impact driving due to changes produced by delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. Current legal thresholds for blood THC while driving are based predominantly on evidence utilizing smoked cannabis. It is known that levels of THC in blood are lower after eating cannabis as compared to smoking yet the impact of edibles on driving and associated blood THC has never been studied.
METHODS
Participants drove a driving simulator before and after ingesting their preferred legally purchased cannabis edible. In a counterbalanced control session, participants did not consume any THC or cannabidiol (CBD). Blood was collected for measurement of THC and metabolites as well as CBD. Subjective experience was also assessed.
RESULTS
Participants consumed edibles with, on average, 7.3 mg of THC, which is less than the maximum amount available in a single retail package in Ontario, providing an ecologically valid test of cannabis edibles. Compared to control, cannabis edibles produced a decrease in mean speed 2 h after consumption but not at 4 and 6 h. Under dual task conditions in which participants completed a secondary task while driving, changes in speed were not significant after the correction for multiple comparison. No changes in standard deviation of lateral position (SDLP; 'weaving'), maximum speed, standard deviation of speed or reaction time were found at any time point or under either standard or dual task conditions. Mean THC levels were significantly increased, relative to control, after consuming the edible but remained relatively low at approximately 2.8 ng/mL 2 h after consumption. Driving impairment was not correlated with blood THC. Subjective experience was altered for 7 h and participants were less willing/able to drive for up to 6 h, suggesting that the edible was intoxicating.
INTERPRETATION
This is the first study of the impact of cannabis edibles on simulated driving. Edibles were intoxicating as revealed by the results of subjective assessments (VAS), and there was some impact on driving. Detection of driving impairment after the use of cannabis edibles may be difficult.
PubMed: 38822413
DOI: 10.1186/s42238-024-00234-y -
Preventive Medicine May 2024Cigarette smoking continues to be a major driver in the incidence and progression of cardiovascular disease (CVD). As females become an increasingly larger fraction of...
OBJECTIVE
Cigarette smoking continues to be a major driver in the incidence and progression of cardiovascular disease (CVD). As females become an increasingly larger fraction of those who smoke it is imperative that the sex-specific effects of smoking be further explored and acted upon.
METHODS
This narrative review describes current evidence on the differential effects of smoking on CVD in females and the need to improve treatment.
RESULTS
Evidence to date suggests that smoking has disproportionately negative effects on the cardiovascular (CV) system in females, especially in those who are younger. Usually, the onset of CVD is later in females than males, but smoking decreases or eliminates this gap. Females are also more likely to develop types of CVD closely tied to smoking, such as ST-elevated myocardial infarctions, with even higher rates among those who are younger. Possible mechanisms for these worse outcomes in females include a complex interplay between nicotine, other products of combusted cigarettes, and hormones. Sex differences also exist in treatment for smoking. In females, Varenicline appears more effective than either Bupropion or nicotine replacement therapy while in males, all three therapies show similar efficacy. Disparities in smoking are also apparent in secondary prevention settings. Females and males are entering secondary prevention with equal rates of smoking, with potentially higher levels of exposure to the byproducts of smoking in females.
CONCLUSIONS
These disproportionately negative outcomes for females who smoke require additional research and these persisting rates of smoking suggest a need for female-specific approaches for treating smoking.
PubMed: 38815766
DOI: 10.1016/j.ypmed.2024.108013 -
Drug Development Research Jun 2024The World Health Organization (WHO) has published a list of priority pathogens that urgently require research to develop new antibiotics. The main aim of the current...
The World Health Organization (WHO) has published a list of priority pathogens that urgently require research to develop new antibiotics. The main aim of the current study is to identify potential marketed drugs that can be repurposed against bacterial infections. A pharmacovigilance-based drug repurposing approach was used to identify potential drugs. OpenVigil 2.1 tool was used to query the FDA Adverse Event Reporting System database. The reporting odds ratio (ROR) < 1, ROR95CI upper bound <1, and no. of cases ≥30 were used for filtering and sorting of drugs. Sunburst plot was used to represent drugs in a hierarchical order using the Anatomical Therapeutic Chemical classification. Molecular docking and dynamics were performed using the Maestro and Desmond modules of Schrodinger 2023 software respectively. A total of 40 drugs with different classes were identified based on the pharmacovigilance approach which has antibacterial potential. The molecular docking results have shown energetically favored binding conformation of lisinopril against 3-deoxy-manno-octulosonate cytidylyltransferase, UDP-2,3-diacylglucosamine hydrolase, and penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa; olmesartan, atorvastatin against lipoteichoic acids flippase LtaA and rosiglitazone and varenicline against d-alanine ligase of Staphylococcus aureus; valsartan against peptidoglycan deacetylase (SpPgdA) and atorvastatin against CDP-activated ribitol for teichoic acid precursors of Streptococcus pneumoniae. Further, molecular dynamic results have shown the stability of identified drugs in the active site of bacterial targets except lisinopril with PBP3. Lisinopril, olmesartan, atorvastatin, rosiglitazone, varenicline, and valsartan have been identified as potential drugs for repurposing against bacterial infection.
Topics: Data Mining; Drug Repositioning; Humans; Molecular Docking Simulation; Pharmacovigilance; Anti-Bacterial Agents; Bacterial Infections; Adverse Drug Reaction Reporting Systems
PubMed: 38807372
DOI: 10.1002/ddr.22211 -
Tobacco Prevention & Cessation 2024Cytisine is a smoking cessation drug now used worldwide. Most of the data available in the literature predict a 25-day treatment, accepted on the basis of previous...
INTRODUCTION
Cytisine is a smoking cessation drug now used worldwide. Most of the data available in the literature predict a 25-day treatment, accepted on the basis of previous clinical experience in Eastern Europe. There are few studies on dosing, and only recently some researchers have tried a longer treatment period.
METHODS
This real-world retrospective cross-sectional study analyzed data collected consecutively from 2015 to 2021, in seven smoking cessation centers in north-central Italy. The aim of this study is to evaluate the effectiveness and tolerability of a 40-day cytisine treatment with an induction phase and a slower reduction schedule. Data were collected from a group of 871 patients treated with cysteine, varenicline, and nicotine replacement therapy (NRT). The sample was not randomized. Behavioral support (4-6 sessions, each lasting 20-30 min, plus the evaluation session) was delivered to all patients.
RESULTS
Subgroups taking cytisine (n=543 for 40 days), varenicline (n=281 for 12 weeks), and NRT (n=47 for eight weeks) showed biochemically confirmed smoking abstinence at 6 months of 50.5%, 55.9%, and 51.0%, respectively, with a statistically significant difference between cytisine versus varenicline (p<0.01) but not between cytisine versus NRT (p=0.5597). Adverse events were 4.4% with cytisine and 33.3% with varenicline. Behavioral support was an important factor in effectiveness.
CONCLUSIONS
This study produced preliminary evidence that the 40-day regimen of cytisine, appears to have less effectiveness in comparison to varenicline but the magnitude of the effect is comparable. The results and tolerability seem to be better than in most other studies.
PubMed: 38803387
DOI: 10.18332/tpc/187556 -
Nicotine & Tobacco Research : Official... May 2024Concerns about safety and effectiveness of tobacco treatments reduce their use. We explored integrating the nicotine metabolite ratio (NMR), and messaging about its...
A Pilot Study to Evaluate the Use of Automated Nicotine Metabolite Ratio Reporting within Primary Care as an Implementation Strategy to Increase the Use of Tobacco Treatments.
INTRODUCTION
Concerns about safety and effectiveness of tobacco treatments reduce their use. We explored integrating the nicotine metabolite ratio (NMR), and messaging about its potential for improving safety and effectiveness, as a strategy to increase use of tobacco treatments within primary care.
METHODS
Through a prospective cohort design, we explored the effects of integrating NMR testing within primary care on the provision of tobacco treatment; 65 patients completed assessments including NMR before a clinic visit. At the clinic visit, patients' clinicians received an electronic health record alert about the patient's NMR and personalized treatment recommendations to improve effectiveness and safety. Being asked about smoking and advised to quit, and a referral for tobacco treatment or medication prescription, were assessed within 30 days of the appointment and were compared to a usual care cohort (N=85).
RESULTS
The NMR and usual care cohorts reported similar rates of being asked about smoking (92.3% vs. 92.9%, p=1.0), being advised to quit (72.3% vs. 74.1%, p=0.85), being referred for tobacco treatment (23.1% vs. 36.5%, p=0.11), and receiving tobacco use medications (20% vs. 27.1%, p=0.34). In the NMR cohort, fast vs. slow metabolizers were more likely to receive medication (26% vs. 0%, p=0.003) and all patients who received varenicline (n=8) were fast metabolizers.
CONCLUSIONS
NMR results and treatment recommendations did not increase tobacco treatment rates in primary care, although it may increase treatment rates and use of varenicline for fast metabolizers. Future studies could test ways to use the NMR to increase tobacco treatment rates in clinical settings.
IMPLICATIONS
This study generated a novel implementation strategy, namely an electronic health record alert about patients' NMR and personalized treatment recommendations, in an effort to increase tobacco treatment rates in primary care. While the strategy did not increase tobacco treatment rates, it may have boosted the rate of varenicline prescription for patients who metabolize nicotine faster, aligning with evidence-based practice.
PubMed: 38779826
DOI: 10.1093/ntr/ntae124 -
The Cochrane Database of Systematic... May 2024In 2020, 32.6% of the world's population used tobacco. Smoking contributes to many illnesses that require hospitalisation. A hospital admission may prompt a quit... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In 2020, 32.6% of the world's population used tobacco. Smoking contributes to many illnesses that require hospitalisation. A hospital admission may prompt a quit attempt. Initiating smoking cessation treatment, such as pharmacotherapy and/or counselling, in hospitals may be an effective preventive health strategy. Pharmacotherapies work to reduce withdrawal/craving and counselling provides behavioural skills for quitting smoking. This review updates the evidence on interventions for smoking cessation in hospitalised patients, to understand the most effective smoking cessation treatment methods for hospitalised smokers.
OBJECTIVES
To assess the effects of any type of smoking cessation programme for patients admitted to an acute care hospital.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 7 September 2022.
SELECTION CRITERIA
We included randomised and quasi-randomised studies of behavioural, pharmacological or multicomponent interventions to help patients admitted to hospital quit. Interventions had to start in the hospital (including at discharge), and people had to have smoked within the last month. We excluded studies in psychiatric, substance and rehabilitation centres, as well as studies that did not measure abstinence at six months or longer.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was abstinence from smoking assessed at least six months after discharge or the start of the intervention. We used the most rigorous definition of abstinence, preferring biochemically-validated rates where reported. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 82 studies (74 RCTs) that included 42,273 participants in the review (71 studies, 37,237 participants included in the meta-analyses); 36 studies are new to this update. We rated 10 studies as being at low risk of bias overall (low risk in all domains assessed), 48 at high risk of bias overall (high risk in at least one domain), and the remaining 24 at unclear risk. Cessation counselling versus no counselling, grouped by intensity of intervention Hospitalised patients who received smoking cessation counselling that began in the hospital and continued for more than a month after discharge had higher quit rates than patients who received no counselling in the hospital or following hospitalisation (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.24 to 1.49; 28 studies, 8234 participants; high-certainty evidence). In absolute terms, this might account for an additional 76 quitters in every 1000 participants (95% CI 51 to 103). The evidence was uncertain (very low-certainty) about the effects of counselling interventions of less intensity or shorter duration (in-hospital only counselling ≤ 15 minutes: RR 1.52, 95% CI 0.80 to 2.89; 2 studies, 1417 participants; and in-hospital contact plus follow-up counselling support for ≤ 1 month: RR 1.04, 95% CI 0.90 to 1.20; 7 studies, 4627 participants) versus no counselling. There was moderate-certainty evidence, limited by imprecision, that smoking cessation counselling for at least 15 minutes in the hospital without post-discharge support led to higher quit rates than no counselling in the hospital (RR 1.27, 95% CI 1.02 to 1.58; 12 studies, 4432 participants). Pharmacotherapy versus placebo or no pharmacotherapy Nicotine replacement therapy helped more patients to quit than placebo or no pharmacotherapy (RR 1.33, 95% CI 1.05 to 1.67; 8 studies, 3838 participants; high-certainty evidence). In absolute terms, this might equate to an additional 62 quitters per 1000 participants (95% CI 9 to 126). There was moderate-certainty evidence, limited by imprecision (as CI encompassed the possibility of no difference), that varenicline helped more hospitalised patients to quit than placebo or no pharmacotherapy (RR 1.29, 95% CI 0.96 to 1.75; 4 studies, 829 participants). Evidence for bupropion was low-certainty; the point estimate indicated a modest benefit at best, but CIs were wide and incorporated clinically significant harm and clinically significant benefit (RR 1.11, 95% CI 0.86 to 1.43, 4 studies, 872 participants). Hospital-only intervention versus intervention that continues after hospital discharge Patients offered both smoking cessation counselling and pharmacotherapy after discharge had higher quit rates than patients offered counselling in hospital but not offered post-discharge support (RR 1.23, 95% CI 1.09 to 1.38; 7 studies, 5610 participants; high-certainty evidence). In absolute terms, this might equate to an additional 34 quitters per 1000 participants (95% CI 13 to 55). Post-discharge interventions offering real-time counselling without pharmacotherapy (RR 1.23, 95% CI 0.95 to 1.60, 8 studies, 2299 participants; low certainty-evidence) and those offering unscheduled counselling without pharmacotherapy (RR 0.97, 95% CI 0.83 to 1.14; 2 studies, 1598 participants; very low-certainty evidence) may have little to no effect on quit rates compared to control. Telephone quitlines versus control To provide post-discharge support, hospitals may refer patients to community-based telephone quitlines. Both comparisons relating to these interventions had wide CIs encompassing both possible harm and possible benefit, and were judged to be of very low certainty due to imprecision, inconsistency, and risk of bias (post-discharge telephone counselling versus quitline referral: RR 1.23, 95% CI 1.00 to 1.51; 3 studies, 3260 participants; quitline referral versus control: RR 1.17, 95% CI 0.70 to 1.96; 2 studies, 1870 participants).
AUTHORS' CONCLUSIONS
Offering hospitalised patients smoking cessation counselling beginning in hospital and continuing for over one month after discharge increases quit rates, compared to no hospital intervention. Counselling provided only in hospital, without post-discharge support, may have a modest impact on quit rates, but evidence is less certain. When all patients receive counselling in the hospital, high-certainty evidence indicates that providing both counselling and pharmacotherapy after discharge increases quit rates compared to no post-discharge intervention. Starting nicotine replacement or varenicline in hospitalised patients helps more patients to quit smoking than a placebo or no medication, though evidence for varenicline is only moderate-certainty due to imprecision. There is less evidence of benefit for bupropion in this setting. Some of our evidence was limited by imprecision (bupropion versus placebo and varenicline versus placebo), risk of bias, and inconsistency related to heterogeneity. Future research is needed to identify effective strategies to implement, disseminate, and sustain interventions, and to ensure cessation counselling and pharmacotherapy initiated in the hospital is sustained after discharge.
Topics: Humans; Smoking Cessation; Randomized Controlled Trials as Topic; Hospitalization; Bias; Counseling; Tobacco Use Cessation Devices; Bupropion; Smoking Cessation Agents; Smoking
PubMed: 38770804
DOI: 10.1002/14651858.CD001837.pub4 -
Heliyon May 2024Smoking is responsible for 80 % of cases of Chronic Obstructive Pulmonary Disease (COPD), while the prognosis is improved by smoking cessation (SC). We examined...
Clinical factors associated with smoking cessation among smokers with Chronic Obstructive Pulmonary Disease by sex: Longitudinal analyses from French smoking cessation services.
BACKGROUND
Smoking is responsible for 80 % of cases of Chronic Obstructive Pulmonary Disease (COPD), while the prognosis is improved by smoking cessation (SC). We examined clinical factors associated with SC among smokers with COPD comparing women and men.
METHODS
The study comprised a cohort of 1470 smokers who visited a SC service and completed at least 28-day of follow-up visits. The outcome was smoking status at follow-up (abstinence, reduction, no change). Abstinence was defined as continuous abstinence for at least 28 days, validated by the measurement of expired Carbon Monoxide. Reduction was defined as a halving of the baseline tobacco consumption.
RESULTS
The average age of the population was 53 (±11) years and 58.2 % were women. Men were 2 years younger than women and consulted more likely after a hospital contact, whereas women consulted on their own initiative. Women more often had a depression history, whereas men had medical comorbidities and co-addictions. There was no significant difference by sex regarding the abstinence rate (41.0 % in women vs 40.7 in men, p > 0.9). The factors significantly associated with higher abstinence rates in both sexes were: at least one previous quit attempt and number of follow-up visits ≥4. The factors negatively associated with quitting in women were diabetes, intake of mood stabilizers and consuming more than 10 cigarettes per day while having a chronic bronchitis, taking antidepressants and having consumed cannabis in the last 30 days hampered SC in men.
CONCLUSIONS
Concerning factors associated with SC, few differences were found between female and male smokers suffering from COPD. However, due to the different medical and smoking behavior characteristics according to sex, it might be important to take these differences into account in order to provide tailored SC management.
PubMed: 38770314
DOI: 10.1016/j.heliyon.2024.e30920 -
American Journal of Preventive Medicine May 2024
PubMed: 38752949
DOI: 10.1016/j.amepre.2024.04.007 -
Journal of Clinical PsychopharmacologyPeople who smoke cigarettes and drink alcohol heavily are less likely to quit smoking compared with those who do not drink heavily. The current study examined the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE/BACKGROUND
People who smoke cigarettes and drink alcohol heavily are less likely to quit smoking compared with those who do not drink heavily. The current study examined the effects of a 12-week treatment phase of combination varenicline and nicotine patch compared with placebo and nicotine patch on smoking cessation (primary outcome) and alcohol consumption (secondary outcome) in heavy drinking smokers at 26-week follow-up.
METHODS/PROCEDURES
Participants were daily smokers who met heavy drinking criteria. They were randomly assigned to receive either varenicline and nicotine patch (n = 61) or placebo and nicotine patch (n = 61) for 12 weeks. At week 26, self-reports of point prevalence cigarette abstinence were biochemically confirmed, and past-month alcohol drinking days and heavy drinking days were assessed.
FINDINGS/RESULTS
At week 26, smoking quit rates did not differ by treatment group (25% varenicline and 26% placebo). Relative to week 12 outcomes, week 26 quit rates significantly dropped off in the varenicline group but not in the placebo group. Alcohol drinking reductions for the whole sample that were previously observed from baseline to week 12 were sustained at week 26, although they did not differ between treatment groups.
IMPLICATIONS/CONCLUSIONS
In heavy drinking smokers, smoking cessation success was evident in a quarter of the total sample at 3 months postmedication discontinuation. At this time, quit rates were the same between those who received varenicline and nicotine patch and those who received nicotine patch alone. Future research is warranted to examine what may aid in longer-term smoking quit rates in heavy drinking smokers.
Topics: Humans; Varenicline; Smoking Cessation; Male; Female; Tobacco Use Cessation Devices; Adult; Middle Aged; Follow-Up Studies; Smoking Cessation Agents; Alcohol Drinking; Drug Therapy, Combination; Treatment Outcome; Nicotinic Agonists; Double-Blind Method
PubMed: 38752924
DOI: 10.1097/JCP.0000000000001864 -
Biochemical Pharmacology Jul 2024Although α2 was the first neuronal nicotinic acetylcholine receptor (nAChR) receptor subunit to be cloned, due to its low level of expression in rodent brain, its study...
Although α2 was the first neuronal nicotinic acetylcholine receptor (nAChR) receptor subunit to be cloned, due to its low level of expression in rodent brain, its study has largely been neglected. This study provides a comparison of the α2 and α4 structures and their functional similarities, especially in regard to the existence of low and high sensitivity forms based on subunit stoichiometry. We show that the pharmacological profiles of the low and high sensitivity forms of α2β2 and α4β2 receptors are very similar in their responses to nicotine, with high sensitivity receptors showing protracted responses. Sazetidine A, an agonist that is selective for the high sensitivity α4 receptors also selectively activates high sensitivity α2 receptors. Likewise, α2 receptors have similar responses as α4 receptors to the positive allosteric modulators (PAMs) desformylflustrabromine (dFBr) and NS9283. We show that the partial agonists for α4β2 receptors, cytisine and varenicline are also partial agonists for α2β2 receptors. Studies have shown that levels of α2 expression may be much higher in the brains of primates than those of rodents, suggesting a potential importance for human therapeutics. High-affinity nAChR have been studied in humans with PET ligands such as flubatine. We show that flubatine has similar activity with α2β2 and α4β2 receptors so that α2 receptors will also be detected in PET studies that have previously presumed to selectively detect α4β2 receptors. Therefore, α2 receptors need more consideration in the development of therapeutics to manage nicotine addiction and declining cholinergic function in age and disease.
Topics: Receptors, Nicotinic; Animals; Nicotinic Agonists; Humans; Nicotine; Xenopus laevis; Azetidines; Quinolizines; Varenicline; Azocines; Quinolizidine Alkaloids; Pyridines
PubMed: 38735444
DOI: 10.1016/j.bcp.2024.116263