Patient interest in acupuncture for smoking cessation: a survey.

BACKGROUND/OBJECTIVE: Tobacco use remains the leading cause of preventable death in the United States. The most widely available treatment options to assist patients in smoking cessation are limited by side effects and moderate efficacy at best. Acupuncture may be an effective option for smoking cessation. The goal of this study was to establish the need for and interest in acupuncture therapy to potentially assist with smoking cessation from a patient perspective. METHODS: We conducted a cross-sectional survey study among patients aged 18 years or older whose medical record reported current tobacco use with English as their preferred language. REDCap surveys were administered to patients during office visits and included questions regarding opinions and use of all treatments available for smoking cessation (including acupuncture) as well as perceived barriers to acupuncture treatment. RESULTS: A total of 57 surveys were distributed, and 42 (74%) were completed. Most patients reported previous attempts at quitting (76%) and had tried a variety of treatments including nicotine replacement (45%), Chantix (varenicline; 23%), Wellbutrin (bupriopion; 19%), "cold turkey" (65%) and hypnosis (3%). No respondents reported having tried acupuncture for smoking cessation. CONCLUSION: When comparing treatment options, patients reported more interest in acupuncture than other treatment options with a statistically significant difference in the level of interest between acupuncture and bupropion. All barriers (cost, time and effectiveness) were equally rated on a Likert-type scale with a median of 50 on a 101-point scale.

The GlyT1-inhibitor Org 24598 facilitates the alcohol deprivation abolishing and dopamine elevating effects of bupropion + varenicline in rats.

Alcohol Use Disorder (AUD) is a relapsing brain disorder that involves perturbations of brain dopamine (DA) systems, and combined treatment with varenicline + bupropion produces additive effects on accumbal DA output and abolishes the alcohol deprivation effect (ADE) in rats. Also, direct and indirect glycine receptor (GlyR) agonists raise basal DA, attenuate alcohol-induced DA release in the nucleus Accumbens (nAc) and reduce alcohol consumption in rats. This study in rats examines whether the GlyT1-inhibitor Org 24598, an indirect GlyR agonist, enhances the ADE-reducing and DA elevating action of the combined administration of varenicline + bupropion in lower doses than previously applied. Effects on voluntary alcohol consumption, the ADE and extracellular levels of glycine and DA in nAc were examined following treatment with Org 24598 6 and 9 mg/kg i.p., bupropion 3.75 mg/kg i.p. and varenicline 1.5 mg/kg s.c., in monotherapy or combined, using a two-bottle, free-choice alcohol consumption paradigm with an ADE paradigm, and in vivo microdialysis in male Wistar rats. Notably, all treatment regimens appeared to abolish the ADE but only the effect produced by the triple combination (Org24598 + varenicline + bupropion) was significant compared to vehicle. Hence, addition of Org 24598 may enhance the ADE-reducing action of varenicline + bupropion and appears to allow for a dose reduction of bupropion. Treatment with Org 24598 raised accumbal glycine levels but did not significantly alter DA output in monotherapy. Varenicline + bupropion produced a substantial elevation in accumbal DA output that was slightly enhanced following addition of Org 24598. Conceivably, the blockade of the ADE is achieved by the triple combination enhancing accumbal DA transmission in complementary ways, thereby alleviating a hypothesized hypodopaminergia and negative reinforcement to drink. Ultimately, combining an indirect or direct GlyR agonist with varenicline + bupropion may constitute a new pharmacological treatment principle for AUD, although further refinement in dosing and evaluation of other glycinergic compounds are warranted.

S3 Guideline "Smoking and Tobacco Dependence: Screening, Diagnosis, and Treatment" - Short Version.

INTRODUCTION: In addition to the prevention of tobacco consumption, the establishment and assurance of high-quality treatment for harmful use and dependence on tobacco products remains an important health-related task in Germany. Regular updating of the Association of the Scientific Medical Societies (AWMF) S3 guideline "Smoking and Tobacco Dependence: Screening, Diagnosis, and Treatment" (Tobacco Guideline) offers a sustainable and reputable source of knowledge on smoking cessation. METHODS: Under the auspices of the German Society for Psychiatry, Psychotherapy, Psychosomatics, and Neurology (DGPPN) and the German Society for Addiction Research and Addiction Therapy (DG-Sucht), the Tobacco Guideline was revised in 2019-2020 by 63 experts, who were involved in the development process of the text, in 11 working groups. Undue influence of conflicts of interest on the guideline could be minimized through careful conflict of interest management. Delegates from 50 professional societies discussed the 80 guideline recommendations and voted online. RESULTS: In addition to recommendations for screening and diagnostics, the Tobacco Guideline takes a positive stance towards the use of low-threshold counseling and support services. If, due to the severity of the tobacco-related disorder, brief counseling, telephone counseling, or internet- or smartphone-based methods are not sufficiently effective, individual or group behavioral therapy, possibly in combination with medication, is indicated. If nicotine replacement therapy is not effective, varenicline or bupropion should be offered. Alternative strategies with a lower level of recommendation are hypnotherapy, mindfulness-based treatments, or medication with cytisine. In adolescents and pregnant women, the use of medication should be limited to well-specified exceptions and nicotine replacement. The mean agreement with the recommendations reached a value of 98%. A general overview of the treatment recommendations of the Tobacco Guideline is provided by three clinical algorithms.

Varenicline as a treatment for cannabis use disorder: A placebo-controlled pilot trial.

BACKGROUND: An efficacious pharmacotherapy for cannabis use disorder (CUD) has yet to be established. This study preliminarily evaluated the safety and efficacy of varenicline for CUD in a proof-of-concept clinical trial. METHODS: Participants in this 6-week randomized, placebo-controlled pilot trial received either varenicline (n = 35) or placebo (n = 37), added to a brief motivational enhancement therapy intervention. Outcomes included cannabis withdrawal, cannabis abstinence, urine cannabinoid levels, percent cannabis use days, and cannabis sessions per day. RESULTS: Both treatment groups noted significant decreases in self-reported cannabis withdrawal, percentage of days used, and use sessions per day during treatment compared to baseline. While this pilot trial was not powered to detect statistically significant between-group differences, participants randomized to varenicline evidenced numerically greater rates of self-reported abstinence at the final study visit [Week 6 intent-to-treat (ITT): Varenicline: 17.1% vs. Placebo: 5.4%; RR = 3.2 (95% CI: 0.7,14.7)]. End-of-treatment urine creatinine corrected cannabinoid levels were numerically lower in the varenicline group and higher in the placebo group compared to baseline [Change from baseline: Varenicline -1.7 ng/mg (95% CI: -4.1,0.8) vs. Placebo: 1.9 ng/mg (95% CI: -0.4,4.3); Δ = 3.5 (95% CI: 0.1,6.9)]. Adverse events related to study treatment did not reveal new safety signals. CONCLUSIONS: Findings support the feasibility of conducting clinical trials of varenicline as a candidate pharmacotherapy for CUD, and indicate that a full-scale efficacy trial, powered based on effect sizes and variability yielded in this study, is warranted.

[Smoking cessation - achievable and effective]. / Tabakentwöhnung ­ wirksam und kosteneffektiv.

In hospital, effective smoking cessation can be organized through counselling, pharmacological aids and, above all, continuous care in outpatient structures following discharge. Pharmacological treatment has proven to be effective and safe with nicotine replacement therapy as well as varenicline. Counselling plus pharmacotherapy is more effective in combination than either therapy is on its own. To better implement structures medical societies in Germany are seeking adequate funding e. g. in the DRG system for hospitalised patients.There are obvious and relevant benefits in smoking cessation. Not only for the main tobacco-related diseases such as coronary heart disease or chronic obstructive pulmonary disease (COPD), positive effects of quitting on morbidity and mortality have been confirmed by high-quality meta-analyses. Furthermore, quality of life is increasing following cessation. Presently, smoking is found to be a significant risk factor for severe disease and mortality following coronavirus infection.Do e-cigarettes offer an alternative in smoking cessation? No. Animal and human data are suggesting toxic effects especially following longer use. The long-term effectiveness of e-cigarettes in tobacco cessation is still uncertain and epidemiologic data clearly point toward ineffectiveness. Furthermore, dual use with potentiation of the toxic effects is common. Therefore, e-cigarettes cannot be recommended for tobacco cessation.

Cytisine versus varenicline for smoking cessation in New Zealand indigenous Maori: a randomized controlled trial.

AIM: To determine whether cytisine was at least as effective as varenicline in supporting smoking abstinence for ≥ 6 months in New Zealand indigenous Maori or whanau (extended-family) of Maori, given the high smoking prevalence in this population. DESIGN: Pragmatic, open-label, randomized, community-based non-inferiority trial. SETTING: Bay of Plenty, Tokoroa and Lakes District Health Board regions of New Zealand. PARTICIPANTS: Adult daily smokers who identified as Maori or whanau of Maori, were motivated to quit in the next 2 weeks, were aged ≥ 18 years and were eligible for subsidized varenicline. Recruitment used multi-media advertising. INTERVENTIONS: A total of 679 people were randomly assigned (1 : 1) to receive a prescription for 12 weeks of cytisine or varenicline, plus low-intensity cessation behavioural support from the prescribing doctor and community stop-smoking services or a research assistant. Day 5 of treatment was the designated quit date. MEASUREMENTS: The primary outcome was carbon monoxide-verified continuous abstinence at 6 months, analysed as intention-to-treat (with multiple imputation for missing data). Secondary outcomes measured at 1, 3, 6 and 12 months post-quit date included: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance and acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. FINDINGS: Verified continuous abstinence rates at 6 months post-quit date were 12.1% (41 of 337) for cytisine versus 7.9% (27 of 342) for varenicline [risk difference 4.29%, 95% confidence interval (CI) = -0.22 to 8.79; relative risk 1.55; 95% CI = 0.97-2.46]. Sensitivity analyses confirmed that the findings were robust. Self-reported adverse events over 6 months occurred significantly more frequently in the varenicline group (cytisine: 313 events in 111 participants; varenicline: 509 events in 138 participants, incidence rate ratio 0.56, 95% CI = 0.49-0.65, P < 0.001) compared with the cytisine group. Common adverse events were headache, nausea and difficulty sleeping. CONCLUSION: A randomized controlled trial found that cytisine was at least as effective as varenicline at supporting smoking abstinence in New Zealand indigenous Maori or whanau (extended-family) of Maori, with significantly fewer adverse events.

Effect of Sustained Smoking Cessation Counseling and Provision of Medication vs Shorter-term Counseling and Medication Advice on Smoking Abstinence in Patients Recently Diagnosed With Cancer: A Randomized Clinical Trial.

Importance: Persistent smoking may cause adverse outcomes among patients with cancer. Many cancer centers have not fully implemented evidence-based tobacco treatment into routine care. Objective: To determine the effectiveness of sustained telephone counseling and medication (intensive treatment) compared with shorter-term telephone counseling and medication advice (standard treatment) to assist patients recently diagnosed with cancer to quit smoking. Design, Setting, and Participants: This unblinded randomized clinical trial was conducted at Massachusetts General Hospital/Dana-Farber/Harvard Cancer Center and Memorial Sloan Kettering Cancer Center. Adults who had smoked 1 cigarette or more within 30 days, spoke English or Spanish, and had recently diagnosed breast, gastrointestinal, genitourinary, gynecological, head and neck, lung, lymphoma, or melanoma cancers were eligible. Enrollment occurred between November 2013 and July 2017; assessments were completed by the end of February 2018. Interventions: Participants randomized to the intensive treatment (n = 153) and the standard treatment (n = 150) received 4 weekly telephone counseling sessions and medication advice. The intensive treatment group also received 4 biweekly and 3 monthly telephone counseling sessions and choice of Food and Drug Administration-approved cessation medication (nicotine replacement therapy, bupropion, or varenicline). Main Outcome and Measures: The primary outcome was biochemically confirmed 7-day point prevalence tobacco abstinence at 6-month follow-up. Secondary outcomes were treatment utilization rates. Results: Among 303 patients who were randomized (mean age, 58.3 years; 170 women [56.1%]), 221 (78.1%) completed the trial. Six-month biochemically confirmed quit rates were 34.5% (n = 51 in the intensive treatment group) vs 21.5% (n = 29 in the standard treatment group) (difference, 13.0% [95% CI, 3.0%-23.3%]; odds ratio, 1.92 [95% CI, 1.13-3.27]; P < .02). The median number of counseling sessions completed was 8 (interquartile range, 4-11) in the intensive treatment group. A total of 97 intensive treatment participants (77.0%) vs 68 standard treatment participants (59.1%) reported cessation medication use (difference, 17.9% [95% CI, 6.3%-29.5%]; odds ratio, 2.31 [95% CI, 1.32-4.04]; P = .003). The most common adverse events in the intensive treatment and standard treatment groups, respectively, were nausea (n = 13 and n = 6), rash (n = 4 and n = 1), hiccups (n = 4 and n = 1), mouth irritation (n = 4 and n = 0), difficulty sleeping (n = 3 and n = 2), and vivid dreams (n = 3 and n = 2). Conclusions and Relevance: Among smokers recently diagnosed with cancer in 2 National Cancer Institute-designated Comprehensive Cancer Centers, sustained counseling and provision of free cessation medication compared with 4-week counseling and medication advice resulted in higher 6-month biochemically confirmed quit rates. However, the generalizability of the study findings is uncertain and requires further research. Trial Registration: ClinicalTrials.gov Identifier: NCT01871506.

Cannabis and Alcohol Co-Use in a Smoking Cessation Pharmacotherapy Trial for Adolescents and Emerging Adults.

INTRODUCTION: The co-use of cannabis and alcohol among tobacco-using youth is common. Alcohol co-use is associated with worse tobacco cessation outcomes, but results are mixed regarding the impact of cannabis on tobacco outcomes and if co-use leads to increased use of non-treated substances. This secondary analysis from a youth smoking cessation trial aimed to (1) evaluate the impact of cannabis or alcohol co-use on smoking cessation, (2) examine changes in co-use during the trial, and (3) explore secondary effects of varenicline on co-use. METHODS: The parent study was a 12-week, randomized clinical trial of varenicline for smoking cessation among youth (ages 14-21, N = 157; Mage = 19, 40% female; 76% White). Daily cigarette, cannabis, and alcohol use data were collected via daily diaries during treatment and Timeline Follow-back for 14 weeks post-treatment. RESULTS: Baseline cannabis co-users (68%) had double the odds of continued cigarette smoking throughout the trial compared with noncannabis users, which was pronounced in males and frequent cannabis users. Continued smoking during treatment was associated with higher probability of concurrent cannabis use. Baseline alcohol co-users (80%) did not have worse smoking outcomes compared with nonalcohol users, but continued smoking was associated with higher probability of concurrent drinking. Varenicline did not affect co-use. CONCLUSIONS: Inconsistent with prior literature, results showed that alcohol co-users did not differ in smoking cessation, whereas cannabis co-users had poorer cessation outcomes. Youth tobacco treatment would benefit from added focus on substance co-use, particularly cannabis, but may need to be tailored appropriately to promote cessation. IMPLICATIONS: Among youth cigarette smokers enrolled in a pharmacotherapy evaluation clinical trial, alcohol and/or cannabis co-use was prevalent. The co-use of cannabis affected smoking cessation outcomes, but more so for males and frequent cannabis users, whereas alcohol co-use did not affect smoking cessation. Reductions in smoking were accompanied by concurrent reductions in alcohol or cannabis use. Substance co-use does not appear to affect all youth smokers in the same manner and treatment strategies may need to be tailored appropriately for those with lower odds of smoking cessation.

Moderators of real-world effectiveness of smoking cessation aids: a population study.

BACKGROUND AND AIMS: Understanding whether and how far smokers' characteristics influence the effectiveness of treatment may be important for tailoring recommendations on cessation aids to those most likely to help the user achieve abstinence. This study aimed to estimate the effectiveness of commonly used smoking cessation aids and test whether their effectiveness differs according to cigarette addiction, socio-economic status, age or sex. DESIGN: Correlational design using cross-sectional survey data collected monthly between 2006 and 2018. SETTING: England. PARTICIPANTS: A total of 18 929 adults (aged ≥ 16 years, 52.0% female) who had smoked within the previous 12 months and had made at least one quit attempt during that period. MEASUREMENTS: The outcome was self-reported abstinence from quit date to survey. Independent variables were self-reported use during the most recent quit attempt of: prescription nicotine replacement therapy (NRT), NRT over-the-counter, varenicline, bupropion, e-cigarettes, face-to-face behavioural support, telephone support, written self-help materials, websites and hypnotherapy. Moderators were cigarette addiction, social grade, age and sex. FINDINGS: After adjustment for covariates and use of other cessation aids, users of e-cigarettes [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.69-2.24] and varenicline (OR = 1.82, 95% CI = 1.51-2.21) had significantly higher odds of reporting abstinence than those who did not report use of these cessation aids. Use of prescription NRT was associated with increased abstinence in older (≥ 45 years) (OR = 1.58, 95% CI = 1.25-2.00) but not younger (< 45 years) smokers (OR = 1.09, 95% CI = 0.85-1.42). Use of websites was associated with increased abstinence in smokers from lower (OR = 2.20, 95% CI = 1.22-3.98) but not higher social grades (OR = 0.74, 95% CI = 0.40-1.38). There was little evidence of benefits of using other cessation aids. CONCLUSIONS: Use of e-cigarettes and varenicline are associated with higher abstinence rates following a quit attempt in England. Use of prescription of nicotine replacement therapy is also associated with higher abstinence rates, but only in older smokers, and use of websites only in smokers from lower socio-economic status.

Varenicline and nabilone in tobacco and cannabis co-users: effects on tobacco abstinence, withdrawal and a laboratory model of cannabis relapse.

Tobacco and cannabis co-users (T+CUs) have poor cannabis cessation outcomes, but the mechanisms underlying this are not well understood. This laboratory study examined the effects of (1) the partial nicotinic agonist, varenicline, on tobacco cessation among T+CUs, and (2) varenicline, alone, and when combined with the cannabinoid agonist nabilone, on cannabis withdrawal and a laboratory model of cannabis relapse. Non-treatment-seeking T+CUs were randomized to active-varenicline or placebo-varenicline, and completed a 15-day outpatient phase; varenicline was titrated to 1 mg BID during days 1-8, and participants were instructed to abstain from tobacco during days 9-15. Participants then moved inpatient for 16 days, where they continued their outpatient medication and tobacco abstinence. Inpatient testing included two, 8-day medication periods, where active-nabilone and placebo-nabilone were administered in counterbalanced order, and measures of acute cannabis effects (days 1-2), withdrawal (days 4-5) and 'relapse' (days 6-8) were collected. Participants in the active-varenicline group were more likely to achieve cotinine-verified tobacco abstinence during the outpatient period versus placebo-varenicline group (46 percent versus 24 percent, respectively), and also reported less mood disturbance and cigarette craving while inpatient. Active-nabilone attenuated cannabis withdrawal in both groups but did not affect cannabis relapse. Regression analyses revealed that two tobacco-related variables, i.e. age of first cigarette use, and cigarette craving while inpatient, were independent predictors of cannabis relapse outcomes. Thus, varenicline holds promise in this population, as a tool to examine the effects of tobacco abstinence on cannabis use outcomes, and as a component of smoking cessation treatments targeting T+CUs.

Diagnosing COPD and supporting smoking cessation in general practice: evidence-practice gaps.

OBJECTIVES: To review the accuracy of diagnoses of chronic obstructive pulmonary disease (COPD) in primary care in Australia, and to describe smokers' experiences with and preferences for smoking cessation. DESIGN, SETTING AND PARTICIPANTS: Patients were invited to participate if they were at least 40 years old and had visited participating general practice clinics in Melbourne at least twice during the previous 12 months, reported being current or ex-smokers with a smoking history of at least 10 pack-years, or were being managed for COPD. Interviews based on a structured questionnaire and case finding (FEV1/FEV6 measurement) were followed, when appropriate, by spirometry testing and assessment of health-related quality of life, dyspnoea and symptoms. RESULTS: 1050 patients attended baseline interviews (February 2015 - April 2017) at 41 practices. Of 245 participants managed for COPD, 130 (53.1%) met the spirometry-based definition (post-bronchodilator FEV1/FVC < 0.7) or had a clinical correlation; in 37% of cases COPD was not confirmed, and no definitive result was obtained for 9.8% of patients. Case finding and subsequent spirometry testing identified 142 new COPD cases (17.6% of participants without prior diagnosis; 95% CI, 15.1-20.5%). 690 participants (65.7%) were current smokers, of whom 360 had attempted quitting during the previous 12 months; 286 (81.0% of those attempting to quit) reported difficulties during previous quit attempts. Nicotine replacement therapy (205, 57.4%) and varenicline (110, 30.8%) were the most frequently employed pharmacological treatments; side effects were common. Hypnotherapy was the most popular non-pharmacological option (62 smokers, 17%); e-cigarettes were tried by 38 (11%). 187 current smokers (27.6%) would consider using e-cigarettes in future attempts to quit. CONCLUSIONS: COPD was both misdiagnosed and missed. Case finding and effective use of spirometry testing could improve diagnosis. Side effects of smoking cessation medications and difficulties during attempts to quit smoking are common. Health professionals should emphasise evidence-based treatments, and closely monitor quitting difficulties and side effects of cessation aids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001155684.

Feasibility and Preliminary Effectiveness of Varenicline for Treating Co-Occurring Cannabis and Tobacco Use.

Few studies have evaluated treatment for co-occurring cannabis and tobacco use. The objective of this pilot study was to evaluate the feasibility and preliminary effectiveness of varenicline for co-occurring cannabis and tobacco use. Participants who reported cannabis use on ≥5 days per week were recruited from an urban, outpatient opioid treatment program (OTP). Participants were randomized to either four weeks of standard OTP clinical care (SCC; medication-assisted treatment for opioid use disorder and individual behavioral counseling), followed by four weeks of SCC plus varenicline (SCC+VT), or to four weeks of SCC+VT followed by four weeks of SCC. All participants contributed feasibility and outcome data during both study phases. Of 193 persons screened, seven were enrolled. Retention at eight weeks was 100%. No adverse effects prompted varenicline discontinuation. Participants reported lower cannabis craving during the SCC+VT phase compared to baseline, and lower frequencies and quantities of cannabis use compared to both baseline and the SCC alone phase. In the SCC+VT phase, participants also reported fewer cigarettes per day. Among persons with co-occurring cannabis and tobacco use, varenicline is well-tolerated and may reduce cannabis craving, cannabis use, and tobacco use.

Cancer-related disease factors and smoking cessation treatment: Analysis of an ongoing clinical trial.

OBJECTIVE: Smoking cessation treatment should be an important aspect of cancer care. In this study, we evaluated whether cancer-related disease factors adversely influence smoking cessation treatment. METHODS: Smokers with cancer (within 5 years of diagnosis, any tumor site) were recruited for an ongoing trial of varenicline for smoking cessation. Disease factors, assessed at baseline, included tumor site, cancer treatment, time since diagnosis, and health-related quality of life. Medication adherence was defined by 132 of 165 pills taken and counseling adherence was defined by 4 of 4 behavioral counseling sessions attended. Abstinence was bioverified at Week 12. Using logistic regression analysis, we assessed the relationship between disease factors and 12-week medication adherence, counseling adherence, and abstinence. RESULTS: Of 144 participants, 56% were medication adherent, 74% were counseling adherent, and 39% were abstinent. Health-related quality of life predicted medication adherence (OR: 1.08, 95% CI, 1.01-1.16, P = .019, d = 0.20) but not counseling adherence or 12-week abstinence. Tumor site, cancer treatment, and time since diagnosis did not predict any smoking cessation treatment outcomes. CONCLUSIONS: Cancer-related disease factors did not predict cancer survivors' engagement or success in smoking cessation treatment. Findings support National Comprehensive Cancer Network Clinical Practice guidelines that recommend smoking cessation treatment for all smokers with cancer, regardless of time since diagnosis.

Using the affective bias test to predict drug-induced negative affect: implications for drug safety.

BACKGROUND AND PURPOSE: Predicting the risk of drug-induced adverse psychiatric effects is important but currently not possible in non-human species. We investigated whether the affective bias test (ABT) could provide a preclinical method with translational and predictive validity. EXPERIMENTAL APPROACH: The ABT is a bowl-digging task, which quantifies biases associated with learning and memory. Rats encounter independent learning experiences, on separate days, under either acute manipulations (e.g. pro-depressant vs. control) or different absolute reward values (e.g. high vs. low). A bias is observed during a preference test when an animal's choices reflect their prior experience. We investigated the effects of putative pro-depressant drug treatments following acute or chronic administration on the formation of an affective bias or reward-induced positive bias respectively. KEY RESULTS: The immunomodulators LPS (10 µg·kg-1 ), corticosterone (10 and 30 mg·kg-1 ) and IFN-α (100 U·kg-1 ) induced a negative affective bias following acute treatment. Tetrabenazine (1 mg·kg-1 ) also induced a negative bias, but no effects were observed with varenicline, carbamazepine or montelukast. Chronic treatment with IFN-α (100 U·kg-1 ) and retinoic acid (10 mg·kg-1 ) impaired the formation of a reward-induced positive bias but did not alter sucrose preference test (SPT). CONCLUSIONS AND IMPLICATIONS: The ABT has the potential to provide a novel approach to predict pro-depressant risk in a non-human species. Negative biases induced by acute treatment in the standard version of the task may also predict longer-term effects on reward processing as shown by the deficit in reward-induced positive bias following chronic treatment, an effect distinct from anhedonia in the SPT. LINKED ARTICLES: This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

Gender differences in the real-world effectiveness of smoking cessation medications: Findings from the 2010-2011 Tobacco Use Supplement to the Current Population Survey.

BACKGROUND: Meta-analyses of clinical trial data have identified clinically relevant gender differences in the efficacy of smoking cessation pharmacotherapy. It is unclear whether these findings are generalizable to smokers quitting in real-world contexts. METHODS: Using Tobacco Use Supplement to the Current Population Survey (TUS-CPS) 2010-2011 cross-sectional data, we generated propensity score matched samples of smokers who quit either unassisted by medication, using only varenicline, or using only transdermal nicotine patch (TNP). We used generalized estimating equations to estimate gender differences in the comparative effectiveness of these cessation options for achieving 30-days of abstinence, adjusting for potential confounders. RESULTS: When stratified by gender, TNP was significantly more effective than unassisted quit attempts for men (OR=1.37; 95%CI=1.02,1.83; p=0.03), but not for women (OR=0.96; 95%CI=0.71,1.31; p=0.82). Varenicline was significantly more effective than unassisted quit attempts for women (OR=1.63; 95%CI=1.16, 2.31; p=0.005), but not men (OR=1.35; 95%CI=0.94,1.96; p=0.11). Varenicline was also more effective than TNP for women (OR=1.51; 95%CI=0.12,2.05; p=0.007) but not men (OR=0.92; 95%CI=0.65,1.31; p=0.64). A significant gender by medication interaction was found only for the comparison of varenicline to TNP (OR=1.64; 95%CI=1.04,2.61; p=0.04). CONCLUSIONS: Findings for varenicline vs. TNP were consistent with clinical trial data, showing greater differences in effectiveness for women compared to men. Results lend support to the generalizability of clinical trial findings, highlighting the importance of considering gender when offering treatment for smoking cessation.

Compromised neuroplasticity in cigarette smokers under nicotine withdrawal is restituted by the nicotinic α4ß2-receptor partial agonist varenicline.

Nicotine modulates neuroplasticity and improves cognitive functions in animals and humans. In the brain of smoking individuals, calcium-dependent plasticity induced by non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) is impaired by nicotine withdrawal, but partially re-established after nicotine re-administration. In order to investigate the underlying mechanism further, we tested the impact of the α4ß2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity in smokers during nicotine withdrawal, induced by PAS and tDCS, respectively. We administered low (0.3 mg) and high (1.0 mg) single doses of varenicline or placebo medication before stimulation over the left motor cortex of 20 healthy smokers under nicotine withdrawal. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes for 36 hours after plasticity induction. Stimulation-induced plasticity was absent under placebo medication, whereas it was present in all conditions under high dose. Low dose restituted only tDCS-induced non-focal plasticity, producing no significant impact on focal plasticity. High dose varenicline also prolonged inhibitory plasticity. These results are comparable to the impact of nicotine on withdrawal-related impaired plasticity in smokers and suggest that α4ß2 nicotinic receptors are relevantly involved in plasticity deficits and restitution in smokers.

Avances y líneas de investigación en el tratamiento y diagnóstico del tabaquismo / Advances research in the treatment and diagnosis of smoking

En el momento actual con el arsenal terapéutico disponible para ayudar a dejar de fumar las tasas de abstinencia se elevan hasta el 50% en el mejor de los casos. Es por ello que estamos en la necesidad de buscar nuevos tratamientos que consigan mejorar las tasas de abstinencia al año, teniendo en cuenta que los fumadores que van quedando son aquellos con una mayor dependencia. Debemos ahondar en el análisis de nuevas posibilidades con la vareniclina. Disponemos de investigación activa en la búsqueda de nuevas dianas terapéuticas como son los agonistas y antagonistas del GABA y del glutamato, receptores de acetilcolina, agonistas serotoninérgicos, inhibidores selectivos de la monoaminooxidasa, y agonistas noradrenérgicos. Por otra parte, el cigarrillo electrónico requiere posicionarse en el momento actual como tratamiento para dejar de fumar, debiendo profundizar en la investigación de las posibilidades de la estimulación intracraneal magnética, el mindfullness y la vacuna antinicotina, además de buscar biomarcadores que consigan unidos una mayor abstinencia

At the present time, the tobacco abstinence rates increase up to 50% with the therapeutic arsenal available, in the best-case scenario. That is why we are in the need for new treatments that achieve higher abstinence rates per year, given that smokers who remain are those with greater dependence. Also, we must give a thorough look into new possibilities for varenicline. There are on-going investigations searching for new therapeutic targets such as agonists and antagonists of GABA and glutamate, acetylcholine receptors, serotonin agonists, selective inhibitors of monoamine oxidase, and noradrenergic agonists. Moreover, the electronic cigarette requires a position at the present time as a treatment for smoking cessation, and other therapeutic approaches like magnetic intracranial stimulation, mindfulness or nicotine vaccine should be explored as well, added to seeking biomarkers in order to obtain higher abstinence with all these combined

Guía práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno mental grave y un trastorno por uso de sustancias / A clinical guideline for the pharmacological and psychological treatment of adult patients with a serious mental disorder and substance use disorder

Objetivos: El objetivo principal de esta Guía es recoger recomendaciones concretas basadas en los resultados de la literatura científica para tratar a pacientes con un trastorno mental grave y un consumo de sustancias atendidos en centros de tratamiento hospitalarios y ambulatorios. Incluye: 1) Recomendaciones farmacológicas y psicológicas para el tratamiento de los pacientes con un un trastorno depresivo mayor y un trastorno por uso de sustancias (cocaína, cannabis, alcohol, nicotina). 2) Recomendaciones farmacológicas y psicológicas para el tratamiento de los pacientes con trastorno del espectro esquizofrénico y un trastorno por uso de sustancias (cocaína, cannabis, alcohol, nicotina). 3) Recomendaciones farmacológicas y psicológicas para el tratamiento de los pacientes con un un trastorno de ansiedad y un trastorno por uso de sustancias (cocaína, cannabis, alcohol, nicotina). 4) Recomendaciones farmacológicas y psicológicas para el tratamiento de los pacientes con un un trastorno bipolar y un trastorno por uso de sustancias (cocaína, cannabis, alcohol, nicotina). 5) Recomendaciones farmacológicas y psicológicas para el tratamiento de los pacientes con un un trastorno por déficit de atención e hiperactividad y un trastorno por uso de sustancias (cocaína, cannabis, alcohol, nicotina).

[Factors associated with success of a smoking cessation program]. / Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario.

BACKGROUND: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. AIM: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. PATIENTS AND METHODS: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. RESULTS: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). CONCLUSIONS: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

Agonistas parciales, moduladores bioquímicos con múltiples aplicaciones / Partial agonists: biochemical modulators with multiple applications

En general, los diferentes tratados de farmacología se organizan en torno a una clasificación anatómica-terapéutica-química. Los tratados de «química farmacéutica» suelen organizarse, además, poniendo énfasis en la naturaleza química de los fármacos, así como en los procesos bioquímicos involucrados en su acción. En otras ocasiones, cuando se contempla la fitoterapia desde un punto de vista botánico, como hace la «botánica medicinal», la exposición se realiza mediante un viaje a través de los diferentes taxones que contienen especies con relevancia terapéutica. En cambio, en este artículo de revisión se va a hablar de un grupo de fármacos que, desde los enfoques expositivos anteriores, no tienen mucho que ver pero que, sin embargo, poseen mecanismos farmacodinámicos muy similares, a pesar de que actúen sobre diferentes receptores. Se trata de los agonistas (y antagonistas) parciales. Lógicamente no se revisarán todos en este artículo, sino aquellos que al autor le han parecido más curiosos e interesantes para ilustrar su relación mutua en cuanto al funcionamiento farmacodinámico: vareniclina, buprenorfina, diazepinonas, aripiprazol, memantina. Este es el objetivo de este artículo: la revisión de un grupo de fármacos desde un punto de vista novedoso, como es su mecanismo de acción farmacodinámico común. Entre las conclusiones, está la indicación de este tipo de fármacos cuando se va a intervenir en sistemas bioquímicos y fisiológicos tan complicados que las funciones a tratar no deben ni inhibirse ni potenciarse desmedidamente, sino simplemente modularse. Este es el caso de muchas dolencias que afectan al sistema nervioso (AU)

In general the different treatises of pharmacology are organised around an anatomical-therapeutic-chemical classification. Treatises about «medicinal chemistry» are organised, not only around this, but also emphasise the chemical nature of the drugs, as well as the biochemical processes involved in their action. Furthermore, when herbal medicine is contemplated from a botanical point of view, as does the «medical botany», exposure is performed by a journey through the different taxa containing species with therapeutic relevance. Nevertheless, in this review article a group of drugs is discussed that, from the previous points of view, do not have anything to do with each other. However, they have very similar pharmacodynamic mechanisms, despite acting on different receptors. These are partial agonists (and antagonists). Obviously not all of these will be reviewed in this article, but those more interesting to illustrate their relationship in terms of pharmacodynamic performance: varenicline, buprenorphine, diazepinones, aripiprazole, memantine. This is the purpose of this article: A review of a group of drugs from a novel point of view, such as their common pharmacodynamic mechanism of action. Among the conclusions, is the indication of these drugs to intervene in such complicated biochemical and physiological systems that functions to be treated should neither be inhibited nor enhanced, but simply modulated. This is the case of many diseases that affect the nervous system (AU)