Self-treatment attempt of tobacco use disorder with Melissa officinalis: a case report and brief review of literature.

In the treatment of tobacco use disorder, current approaches focus on pharmacotherapy, nicotine replacement, and psychotherapy. However, traditional treatments have been widely used in societies for the purpose of smoking cessation for years. Although cases using traditional herbs in the self-treatment of addiction have been reported in the literature, studies on this subject are very limited. Research on certain herbs shows that they may be effective in the treatment of tobacco use disorder by different mechanisms, however, there is no evidence that they are safe to consume as cigarettes. This article aims to question the place of traditional herbs in tobacco use disorder treatment through a case who started to smoke Melissa officinalis herb to help his nicotine withdrawal.

Classic Psychedelics in Addiction Treatment: The Case for Psilocybin in Tobacco Smoking Cessation.

This manuscript reviews research suggesting that classic psychedelics (5-HT2A receptor agonists) are effective in treating addictions including tobacco use disorder. I review historical research from the 1950s to 1970s suggesting that classic psychedelics are associated with addiction recovery across pharmacologically distinct drugs of addiction. I then review anthropological reports about ceremonial use of classic psychedelics and epidemiological studies that are consistent with anti-addiction efficacy. I review modern research using psilocybin in the treatment of alcohol use disorder and tobacco use disorder. Both lines of research show high success rates in preliminary studies. General anti-addiction efficacy across a variety of classes of addictive drugs is consistent with the notion that the persisting positive behavior change prompted by psychedelic therapy is due to amplification of psychotherapeutic processes. Future research should examine classic psychedelic treatment of additional substance use disorders including for opioids, cocaine, methamphetamine, and cannabis, and other disorders broadly characterized as addictions (e.g., obesity, problem gambling, hypersexual disorder). Future research should also explore addiction treatments with other classic psychedelics including LSD, mescaline, DMT, 5-MeO-DMT, and yet-to-be-discovered compounds. Experimental research is also needed to test different protocols for the delivery of classic psychedelic therapy for addictions. Given the staggering society costs of substance use disorders, including the mortality caused by tobacco smoking, it is critical that public funding be made available for scientists to follow up on promising early findings of classic psychedelics in addiction treatment. The costs and risks of not conducting such research are too great.

The effect of vitamin D supplementation on tobacco-related disorders in individuals with a tobacco use disorder: a randomized clinical trial.

Vitamin D deficiency in cigarette smokers (CS) might associate with several complications, including metabolic deficits, depression and anxiety. This study evaluated the effects of vitamin D on mental health symptoms, nicotine misuse, and biomarkers of metabolic diseases in individuals with a tobacco use disorder. A randomized, double-blind, placebo-controlled trial was conducted with 60 CS subjects receiving either 50,000 IU vitamin D supplements (n = 30) or placebo (n = 30) every 2 weeks for 24-weeks. Nicotine misuse, mental health scale, and metabolic parameters were measured before and after the intervention in the CS subjects. Compared with the placebo-group, after the 24-weeks intervention, serum 25 (OH) vitamin D levels increased in the intervention group (ß 2.96; 95% CI, 0.91, 5.01; P = 0.006). In addition, vitamin D supplementation significantly improved Beck Depression Inventory (BDI) (ß -2.06; 95% CI, -3.84, -0.28; P = 0.02). In addition, vitamin D administration significantly decreased fasting plasma glucose (FPG) (ß -4.56; 95% CI, -8.94, -0.19; P = 0.04), insulin (ß -0.50; 95% CI, -0.88, -0.13; P = 0.009), and homeostasis model of assessment-estimated insulin resistance (HOMA-IR) levels (ß -0.21; 95% CI, -0.33, -0.08; P = 0.001). Furthermore, vitamin D resulted in a significant elevation in total antioxidant capacity (TAC) (ß 81.20; 95% CI, 18.30, 144.11; P = 0.01), and plasma glutathione (GSH) levels (ß 73.05; 95% CI, 18.56, 127.54; P = 0.01), compared with the placebo-group. Administration of vitamin D for 24-weeks to CS subjects had beneficial effects on symptoms of depression and several metabolic biomarkers. While this preliminary study suggests that vitamin D might have beneficial effects, its clinical efficacy in individuals with a tobacco use disorder should be further validated in future clinical trials.

Linalool attenuates acquisition and reinstatement and accelerates the extinction of nicotine-induced conditioned place preference in male mice.

Background: Nicotine is the addictive agent in tobacco products. The monoterpene linalool is the main ingredient in the essential oils of various aromatic plants. It has previously been demonstrated that linalool has beneficial effects on some mechanisms that are important in drug addiction.Objectives: The goal of the current study was to investigate the effect of linalool on nicotine-induced conditioned place preference (CPP) in male mice.Methods: CPP was induced by administering intraperitoneal (i.p.) injection of nicotine (0.5 mg/kg) during the conditioning phase. The effects of nicotinic acetylcholine receptor partial agonist varenicline and linalool on the rewarding characteristics of nicotine were tested in mice with administration of linalool (12.5, 25, and 50 mg/kg, i.p.), varenicline (2 mg/kg, i.p.) or saline 30 minutes before nicotine injection. CPP was extinguished by repeated testing, during which conditioned mice were administered varenicline and linalool every day. One day after the last extinction trial, mice that received linalool, varenicline or saline 30 minutes before a priming injection of nicotine (0.1 mg/kg, i.p.) were immediately tested for reinstatement of CPP.Results: Linalool attenuated nicotine acquisition (50 mg/kg, p < .01) and reinstatement (25 and 50 mg/kg, respectively p < .05, p < .01) and accelerated the extinction of nicotine-induced CPP (50 mg/kg, p < .05). Linalool exhibited similar effects on the reference drug varenicline in the CPP phases.Conclusion: These results suggest that linalool may be helpful as an adjuvant for the treatment of nicotine use disorder.

Inhibition of monoacylglycerol lipase reduces nicotine reward in the conditioned place preference test in male mice.

Nicotine, the primary psychoactive component in tobacco, plays a major role in the initiation and maintenance of tobacco dependence and addiction, a leading cause of preventable death worldwide. An essential need thus exists for more effective pharmacotherapies for nicotine-use cessation. Previous reports suggest that pharmacological and genetic blockade of CB1 receptors attenuate nicotine reinforcement and reward; while exogenous agonists enhanced these abuse-related behaviors. In this study, we utilized complementary genetic and pharmacologic approaches to test the hypothesis that increasing the levels of the endocannabinoid 2-arachindonoylglycerol (2-AG), will enhance nicotine reward by stimulating neuronal CB1 receptors. Contrary to our hypothesis, we found that inhibition of monoacylglycerol lipase (MAGL), the primary catabolic enzyme of 2-AG, attenuates nicotine conditioned place preference (CPP) in mice, through a non-CB1 receptor-mediated mechanism. MAGL inhibition did not alter palatable food reward or Lithium Chloride (LiCl) aversion. In support of our findings, repeated MAGL inhibition did not induce a reduction in CB1 brain receptor levels or hinder function. To explore the potential mechanism of action, we investigated if MAGL inhibition affected other fatty acid levels in our CPP paradigm. Indeed, MAGL inhibition caused a concomitant decrease in arachidonic acid (AA) levels in various brain regions of interest, suggesting an AA cascade-dependent mechanism. This idea is supported by dose-dependent attenuation of nicotine preference by the selective COX-2 inhibitors valdecoxib and LM-4131. Collectively, these findings, along with our reported studies on nicotine withdrawal, suggest that inhibition of MAGL represents a promising new target for the development of pharmacotherapies to treat nicotine dependence.

Preclinical and clinical research on the discriminative stimulus effects of nicotine.

Across species, nicotine can produce robust discriminative stimulus (DS) effects, as with other drugs of abuse, a feature that has been harnessed to advance our understanding on the neuropharmacological mechanisms of nicotine's actions. With the crucial role played by nicotine in supporting tobacco dependence, nicotine DS effects have presented an ideal platform to develop novel generation of smoking cessation compounds. Findings from preclinical strands of research have invigorated the field of human discrimination research to objectively assess nicotine's interoceptive stimulus effects. As such, translation studies provide proof of concept for nicotine DS research as a method to assess the subjective effects of nicotine per se, separate from non-nicotine stimuli involved in smoking. Recent clinical studies with low doses have demonstrated that perceiving nicotine's DS effects is necessary, yet not sufficient, for that dose to be reinforcing. These measures have been instrumental in developing novel strategies with regards to establishing threshold doses of nicotine contained in tobacco products, to then determine subthreshold doses that cannot be discriminated and, therefore, fail to maintain reinforcement. Findings from preclinical and clinical nicotine DS research could substantially inform public health policies aimed at regulating nicotine content of consumer products so that they minimize risks of dependency. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.

A Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of a Nicotine Mint Lozenge (2 and 4 mg) in Smoking Cessation.

OBJECTIVE: To evaluate the efficacy in smoking cessation and safety of 2 and 4 mg nicotine mint lozenges in Chinese adult smokers. METHODS: This was a multicenter, randomized, stratified, double-blind, placebo-controlled, parallel-group study. The low-dependence stratum included 483 smokers (241 randomized to active 2 mg nicotine lozenge and 242 to placebo lozenge). The high-dependence stratum included 240 smokers (120 randomized to active 4 mg nicotine lozenge and 120 to placebo lozenge). The primary endpoint was successful smoking cessation at 6 weeks postquit, defined as continuous abstinence from smoking for the 28-day period up to and including the 6-week visit (verified by CO measurement). Cochran-Mantel-Haenszel tests were performed to compare quit rates between active nicotine and placebo separately for the high-dependence and low-dependence strata. RESULTS: The primary analysis showed that in the low-dependence (2 mg) stratum, 59 subjects (24.5%) of 241 in the active nicotine group and 52 subjects (21.5%) of 242 in the placebo group were successful quitters (P = .3851). In the high-dependence (4 mg) stratum, 37 subjects (30.8%) of 120 in the active nicotine group and 24 subjects (20.2%) of 119 in the placebo group were successful quitters (P = .0565). CONCLUSIONS: The 4 mg nicotine lozenge provided a directionally significant improvement in smoking cessation rates compared with placebo in Chinese adult smokers with high nicotine dependence for the primary endpoint. The 2 mg nicotine lozenge provided higher, but nonsignificant, smoking cessation rates than placebo. Both nicotine lozenges were generally well tolerated in Chinese adult smokers.

Novel Mineral-Vitamin Treatment for Reduction in Cigarette Smoking: A Fully Blinded Randomized Placebo-Controlled Trial.

INTRODUCTION: Many smokers do not achieve abstinence using current smoking cessation options. This randomized controlled trial (RCT) investigated a novel nutritional supplement to assist with quitting smoking. METHODS: Following a baseline phase where cigarettes per day and nicotine dependence were measured, participants (n = 107) were randomized to placebo (n = 50) or micronutrient conditions (n = 57). A 4-week pre-quit phase permitted titration up to 12 capsules/day. During the quit phase (12 weeks), participants were registered with a public Quitline while consuming micronutrients or placebo. Carbon monoxide levels were measured to confirm smoking cessation. RESULTS: Forty-five (42%) participants completed the trial. Treatment and placebo groups did not differ on the primary outcome of continuous abstinence at 12 weeks using intention-to-treat analysis; however, 28% of the micronutrient-treated group had quit versus 18% for placebo (odds ratio [OR] = 1.78, 95% confidence interval [CI] = 0.71 to 4.48), with number needed to treat = 10. Comparison of cigarette consumption (cigarettes per day) between micronutrient and placebo groups showed that those taking micronutrients reported reduced consumption throughout the trial, notably at pre-quit weeks 1 and 4, and at quit phase week 4. There were no serious adverse events, blinding was successful, and there were no substantive group differences in side effects or dropout rate. CONCLUSION: This is the first RCT investigating the impact of micronutrients on smoking reduction, finding that micronutrients reduced harm through reduction in number of cigarettes smoked relative to placebo. The small sample and high dropout rate limit confidence in the conclusions and generalizability of the study; however, assessed by number needed to treat, micronutrients are comparable to other smoking cessation treatments but with fewer side effects. Future research using larger and longer trials including cost-effectiveness and biomarker measures is encouraged. IMPLICATIONS: Micronutrients are being increasingly studied for the treatment of psychiatric conditions, but direct application of micronutrients as a treatment for addictions is novel. There is extensive evidence that micronutrients alleviate stress. Given that tobacco smoking is often used to cope with stress, taking micronutrients may moderate the stress of withdrawal and increase the chance of a successful quit attempt. This study is the first known RCT to investigate the use of micronutrients to support smoking cessation. Treatments that are safe, effective, relatively inexpensive, and readily available are needed and micronutrient supplements offer one such possible alternative.

Vitexin as an active ingredient in passion flower with potential as an agent for nicotine cessation: vitexin antagonism of the expression of nicotine locomotor sensitization in rats.

CONTEXT: Nicotine, a bioactive component of tobacco, is highly addictive. Numerous therapies have been developed for smoking cessation, and all have met with limited success. Our laboratory has previously shown that an extract of Passiflora incarnata Linn. (Passifloraceae) antagonized the expression of nicotine locomotor sensitization in rats. OBJECTIVE: This study examined the ability of vitexin, a flavonoid found in P. incarnata, to ameliorate the signs of nicotine sensitization in rats. MATERIALS AND METHODS: Male Wistar rats were administered 0.4 mg/kg nicotine or vehicle (n = 16-18 per group) once a day for four consecutive days. Nicotine administration produces sensitization of locomotor activity. On the fifth day, locomotor activity was monitored as rats from each treatment group were administered either 30 or 60 mg/kg vitexin or its vehicle (n = 4-6 per group) 30 min before a challenge dose of 0.4 mg/kg nicotine. RESULTS: The challenge dose of nicotine resulted in locomotor activity in rats sensitized to nicotine for 4 days that was approximately twice that measured in rats treated with vehicle during the sensitization phase. Rats sensitized to nicotine and then treated with 60 mg/kg vitexin prior to the nicotine challenge exhibited a level of locomotor activity equivalent to the vehicle-treated controls. DISCUSSION: Vitexin antagonized the expression of nicotine locomotor sensitization in rats as the whole extract did in the previous study. CONCLUSION: Vitexin should be examined in future studies to evaluate its potential for treating nicotine addiction in humans.

Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients.

BACKGROUND: A 239-question cross-sectional survey was sent out via email in January 2017 to gather comprehensive information on cannabis use from Canadian medical cannabis patients registered with a federally authorized licensed cannabis producer, resulting in 2032 complete surveys. METHODS: The survey gathered detailed demographic data and comprehensive information on patient patterns of medical cannabis use, including questions assessing the self-reported impact of cannabis on the use of prescription drugs, illicit substances, alcohol, and tobacco. RESULTS: Participants were 62.6% male (n = 1271) and 91% Caucasian (n = 1839). The mean age was 40 years old, and pain and mental health conditions accounted for 83.7% of all respondents (n = 1700). Then, 74.6% of respondents reported daily cannabis use (n = 1515) and mean amount used per day was 1.5 g. The most commonly cited substitution was for prescription drugs (69.1%, n = 953), followed by alcohol (44.5%, n = 515), tobacco (31.1%, n = 406), and illicit substances (26.6%, n = 136). Opioid medications accounted for 35.3% of all prescription drug substitution (n = 610), followed by antidepressants (21.5%, n = 371). Of the 610 mentions of specific opioid medications, patients report total cessation of use of 59.3% (n = 362). CONCLUSIONS: This study offers a unique perspective by focusing on the use of a standardized, government-regulated source of medical cannabis by patients registered in Canada's federal medical cannabis program. The findings provide a granular view of patient patterns of medical cannabis use, and the subsequent self-reported impacts on the use of opioids, alcohol, and other substances, adding to a growing body of academic research suggesting that increased regulated access to medical and recreational cannabis can result in a reduction in the use of and subsequent harms associated with opioids, alcohol, tobacco, and other substances.

Quit Intentions Moderate Subjective and Physiological Responses to Acute Nicotine Replacement Therapy Administration in Dependent Smokers.

INTRODUCTION: This study assessed the impact of expectancy and administration components of acute nicotine inhaler use on craving, heart rate, and smoking behavior in smokers with varying intentions to quit. METHODS: 47 dependent smokers that differed in self-reported intention to quit (no intention to quit during the next month N = 26 vs. intention to initiate a quit attempt within 2 weeks N = 21) were randomly administered a 4 mg nicotine or nicotine-free inhaler across two sessions. Instructions regarding the inhaler's nicotine content (expect nicotine vs. expect nicotine-free; nicotine expectancy) and flavor (mint vs. citrus) varied across sessions. Craving and heart rate were assessed before and after inhaler administration (two-second inhalations every 10 seconds over 20 minutes). Next, participants were offered an opportunity to self-administer puffs of their preferred tobacco brand during an hour-long progressive ratio task. RESULTS: Across participants, nicotine expectancy independently reduced withdrawal related craving (p = .018), but no comparable effects of nicotine administration were evident. In quitting motivated smokers, nicotine expectancy and administration interacted to reduce intention to smoke (p = .040), while nicotine expectancy (p = .047) and administration (p = .025) independently reduced intention to smoke in quitting unmotivated smokers. Blunted heart rate reactivity to nicotine administration was observed in quitting motivated relative to unmotivated smokers (p = .042); however, neither expectancy nor administration impacted smoking behavior in either group (p values > .25). CONCLUSIONS: Findings indicate that participant quitting intentions moderate acute nicotine replacement therapy responses. In quitting motivated smokers, a combination of pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving. IMPLICATIONS: Findings from this study demonstrate that motivations to quit smoking moderate subjective and physiological responses to acute nicotine administration and expectancy in dependent cigarette smokers. Quitting motivated smokers showed blunted heart rate reactivity to nicotine administration, suggesting that they may be less sensitive to the rewarding aspects of nicotine consumption. Nicotine administration and expectancy were found to interact to reduce craving in quitting motivated but not in unmotivated smokers, suggesting that pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving in smokers who plan to quit.

Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal in mice.

The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitary-adrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction.

Impacto da suplementação com ácidos graxos ômega-3 nas subfrações da lipoproteína de alta densidade de indivíduos tabagistas / Impact of omega-3 fatty acid supplementation on high density lipoprotein subfractions of smokers

RESUMO Objetivo Avaliar o efeito da suplementação com ômega-3 nas subfrações das lipoproteínas de alta densidade em indivíduos tabagistas. Métodos Ensaio clínico, randomizado, duplo-cego. Foi selecionada uma amostra com 33 tabagistas, de ambos os sexos, com idade entre 30 e 60 anos, suplementados com ômega-3 (n=17) ou placebo (ácidos graxos ômega-6, n=16) por dois meses. As subfrações das lipoproteínas de alta densidade foram analisadas pelo sistema Lipoprint. Os testes estatísticos foram realizados com o auxílio do programa Statistical Package for the Social Sciences, versão 20.0. Resultados A média de idade foi 49 anos, com predominância da raça branca. Após a intervenção, o grupo ômega-3 modificou positivamente o perfil lipídico e as subfrações das lipoproteínas de alta densidade dos tabagistas. Nos modelos de regressão linear testados, o percentual de ácido docosahexaenoico plasmático apresentou associações negativas com o percentual das lipoproteínas de alta densidade-pequena. Conclusão A suplementação com ômega-3 está associada a uma alteração favorável na distribuição das subfrações das lipoproteínas de alta densidade, aumentando as lipoproteínas de alta densidade-grande e diminuindo as lipoproteínas de alta densidade-pequena. Isso reforça a importância do ômega-3 na saúde cardiovascular de indivíduos tabagistas.

ABSTRACT Objective To assess the effect of omega-3 supplementation on smokers' high density lipoprotein subfractions. Methods This randomized, double-blind clinical trial included 33 male and female smokers aged 30 to 60 years. The sample took omega-3 fatty acids (n=17) or placebo (omega-6 fatty acids, n=16) for two months. The Lipoprint system analyzed the high density lipoprotein subfractions. The statistical tests were performed by the software Statistical Package for the Social Sciences, version 20.0. Results The mean age of the sample was 49 years, and most individuals were white. After the intervention, the lipid profile and high density lipoprotein subfractions of the omega-3 group improved. In the tested linear regression models, the percentage of plasma docosahexaenoic acid was negatively associated with the percentage of small high density lipoprotein. Conclusion Omega-3 supplementation is associated with a favorable change in the distribution of high density lipoprotein subfractions, increasing the large and reducing the small high density lipoproteins. This finding reinforces the importance of omega-3 fatty acids for smokers' cardiovascular health.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

BACKGROUND AND OBJECTIVE: Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS: Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS: Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).

Inhibition effects of Vernonia cinerea active compounds against cytochrome P450 2A6 and human monoamine oxidases, possible targets for reduction of tobacco dependence.

The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Vernonia cinerea, a medicinal plant commonly used for treatment of diseases such as asthma and bronchitis, has been shown reducing tobacco dependence effect among tobacco users. In the present study, we found eight active compounds isolated from V. cinerea that comprise inhibitory activity toward CYP2A6 and MAO-A and MAO-B enzymes using activity-guided assays, with coumarin as substrate of CYP2A6 and kynuramine of MAOs. These compounds were three flavones (apigenin, chrysoeriol, luteolin), one flavonol (quercetin), and four hirsutinolide-type sesquiterpene lactones (8α-(2-methylacryloyloxy)-hirsutinolide-13-O-acetate, 8α-(4-hydroxymethacryloyloxy)-hirsutinolide-13-O-acetate, 8α-tigloyloxyhirsutinolide-13-O-acetate, and 8α-(4-hydroxytigloyloxy)-hirsutinolide-13-O-acetate). Modes and kinetics of inhibition against the three enzymes were determined. Flavonoids possessed strong inhibitory effect on CYP2A6 in reversible mode, while inhibition by hirsutinolides was mechanism-based (NADPH-, concentration-, and time-dependence) and irreversible. Inhibition by hirsutinolides could not be reversed by dialysis and by addition of trapping agents or potassium ferricyanide. Flavonoids inhibited MAOs with variable degrees and were more prominent in inhibition toward MAO-A than hirsutinolides, while two of hirsutinolides inhibited MAO-B approximately comparable to two flavonoids. These results could have implications in combination of drug therapy for smoking cessation.

Acceptance and commitment therapy smoking cessation treatment for veterans with posttraumatic stress disorder: a pilot study.

OBJECTIVE: Veterans with PTSD smoke at rates two to three times higher than the general population, while their quit rate is less than half that of the general population. The present study evaluated the feasibility, acceptability, and preliminary efficacy of Acceptance and Commitment Therapy for Veterans With Posttraumatic Stress Disorder (PTSD) and Tobacco Addiction (ACT-PT), which focuses on helping veterans overcome emotional challenges to quitting smoking. METHODS: Veterans with current PTSD who smoked 15 or more cigarettes/day (N = 19) participated in an open trial of ACT-PT. Participants attended nine weekly individual counseling sessions and received eight weeks of nicotine patch therapy. Primary outcomes included feasibility and acceptability of the intervention, and secondary outcomes included expired-air carbon monoxide confirmed seven-day point prevalence abstinence, cravings, and PTSD symptoms. RESULTS: The retention rate for ACT-PT was good (74%) and client satisfaction ratings were high. Participants made multiple quit attempts (M = 3.6, SD = 4.2) during the study period and were significantly more confident that they could quit smoking at three-month follow-up. At the end of treatment, 37% of participants were abstinent from smoking and 16% were abstinent at three-month follow-up. Overall, participants reduced their smoking by 62% at the end of treatment and 43% at three-month follow-up. PTSD symptoms and smoking urges significantly decreased from baseline to the end of treatment and three-month follow-up. CONCLUSIONS: ACT-PT appears to be a promising smoking cessation treatment for veterans with PTSD. Future research should evaluate ACT-PT in a randomized controlled trial.

Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain.

Chronic nicotine administration increases the density of brain α4ß2* nicotinic acetylcholine receptors (nAChRs), which may contribute to nicotine addiction by exacerbating withdrawal symptoms associated with smoking cessation. Varenicline, a smoking cessation drug, also increases these receptors in rodent brain. The maintenance of this increase by varenicline as well as nicotine replacement may contribute to the high rate of relapse during the first year after smoking cessation. Recently, we found that sazetidine-A (saz-A), a potent partial agonist that desensitizes α4ß2* nAChRs, does not increase the density of these receptors in brain at doses that decrease nicotine self-administration, increase attention in rats, and produce anxiolytic effects in mice. Here, we investigated whether chronic saz-A and varenicline maintain the density of nAChRs after their up-regulation by nicotine. In addition, we examined the effects of these drugs on a measure of anxiety in mice and weight gain in rats. After increasing nAChRs in the rodent brain with chronic nicotine, replacing nicotine with chronic varenicline maintained the increased nAChR binding, as well as the α4ß2 subunit proteins measured by western blots. In contrast, replacing nicotine treatments with chronic saz-A resulted in the return of the density of nAChRs to the levels seen in saline controls. Nicotine, saz-A and varenicline each demonstrated anxiolytic effects in mice, but only saz-A and nicotine attenuated the gain of weight over a 6-week period in rats. These findings suggest that apart from its modest anxiolytic and weight control effects, saz-A, or drugs like it, may be useful in achieving long-term abstinence from smoking.

Tobacco dependence curricula in US osteopathic medical schools: a follow-up study.

CONTEXT: Tobacco use is the leading preventable cause of illness and death in the United States. A 1998 survey of US osteopathic medical schools identified deficiencies in tobacco dependence curricula. OBJECTIVE: To assess the current content and extent of tobacco dependence education and intervention skills in US osteopathic medical school curricula. DESIGN: An electronic survey. SETTING: Osteopathic medical schools with students enrolled for the 2009-2010 academic year. PARTICIPANTS: Twenty-seven osteopathic medical school deans or their designated administrators. MAIN OUTCOME MEASURES: Reported instruction in 7 basic science and 6 clinical science content areas (elective or required) and hours of tobacco dependence education were assessed and compared with the 1998 data. RESULTS: The mean (standard deviation) number of content areas reported as covered in 2010 was 10.6 (2.3) (6.1 [1.2] basic science areas, 4.6 [1.3] clinical science areas). Seventeen of 27 respondents (63%) reported that smokeless tobacco content was covered at their school, and 9 of 27 (33%) reported that the stages of change counseling technique was covered. Compared with 1998, a significant increase was noted in the percentage of schools covering tobacco dependence (92.6% in 2010 compared with 57.9% in 1998, P=.0002). Reported hours of tobacco dependence instruction were also significantly higher in 2010 compared with those in 1998 (Fisher exact test, P<.05). No statistically significant changes were found in the proportion of schools covering all 13 content areas (15.7% vs 22.2%), the proportion covering motivational interviewing in detail (26.3% vs 33.3%), or the proportion requiring curricula on smokeless tobacco (57.9% vs 59.3%). CONCLUSION: Osteopathic medical school respondents reported more instruction on tobacco dependence in 2010 compared with those in 1998. However, some important basic science and clinical science content areas are not being adequately taught in US osteopathic medical schools.

Use of micronutrients attenuates cannabis and nicotine abuse as evidenced from a reversal design: a case study.

Prior research shows that micronutrients, particularly amino acids, can assist individuals with substance dependence to quit various drugs of abuse, including cannabis, alcohol, and cocaine. As part of a wider investigation of the impact of micronutrients (mostly vitamins and minerals) on psychiatric symptoms, such as Attention-Deficit/Hyperactivity Disorder (ADHD), depression, and anxiety, we observed that many participants reduced or eliminated use of alcohol, cigarettes, and cannabis. One case using a single-case reversal (off-on-off-on-off) design is presented and shows not only on-off control of psychiatric symptoms as micronutrients are consumed or withdrawn, but also simultaneous on-off use of cannabis and cigarettes, despite not directly targeting this substance use as part of the treatment protocol. This case adds to a growing body of research supporting the use of micronutrients in the treatment of psychiatric symptoms and suggests it may extend to substance dependence. Micronutrients, by assisting with mood regulation and reductions in anxiety, may assist with successful cessation of drug use. Alternatively, they may directly impact on the brain reward circuitry believed to be involved in the expression of addictions, thereby providing the appropriate precursors and cofactors necessary for adequate neurotransmitter synthesis. This case should continue to stimulate researchers to consider the role of nutrients, in particular vitamins and minerals, in drug treatment programs and encourage more rigorous trials.