Nicotine

Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes ...

Despite the wide-ranging and authoritative 1988 review by the US Surgeon General, views questioning the addictiveness of nicotine contine to be expressed in some quarters. This lack of complete consensus is not unexpected, since no universally agreed scientific definition of addiction exists. In this paper we briefly consider a number of lines of evidence from both the human and animal literature bearing on the addictiveness of nicotine. Patterns of use by smokers and the remarkable intractability of the smoking habit point to compulsive use as the norm. Studies in both animal and human subjects have shown that nicotine can function as reinforcer, albeit under a more limited range of conditions than with some other drugs of abuse. In drug discrimination paradigms there is some cross-generalisation between nicotine on the one hand, and amphetamine and cocaine on the other. A welldefined nicotine withdrawal syndrome has been delineated which is alleviated by nicotine replacement. Nicotine replacement also enhances outcomes in smoking cessation, roughly doubling success rates. In total, the evidence clearly identifies nicotine as a powerful drug of addiction, comparable to heroin, cocaine and alcohol.

The health consequences of tobacco smoking disproportionately affect African Americans, but research on whether efficacious interventions can be generalized to this population is limited. This study examined the efficacy of group-based cognitive-behavioral therapy (CBT) for smoking cessation among African Americans. Method: Participants (N ϭ 154; 65% female, M ϭ 44 years old, mean cigarettes/ day ϭ 13) were randomly assigned to either (a) group CBT or (b) group general health education (GHE). Participants in both conditions received 6 sessions of counseling and 8 weeks of transdermal nicotine patches. The primary outcome variable was 7-day point prevalence abstinence (ppa), assessed at the end of counseling (2 weeks) and at 3-and 6-month follow-ups. Secondary outcomes included 24-hr ppa and 28-day continuous abstinence (assessed at 3 and 6 months). Results: Intent-to-treat analyses demonstrated the hypothesized effects, such that 7-day ppa was significantly greater in the CBT than the GHE condition at the end of counseling (51% vs. 27%), at 3 months (34% vs. 20%), and at 6 months (31% vs. 14%). Results of a generalized linear mixed model demonstrated a significant effect of CBT versus GHE on 7-day ppa (odds ratio ϭ 2.57, 95% CI [1.40, 4.71] and also an effect of time ( p Ͻ .002). The Condition ϫ Time interaction was not significant. Similar patterns of results emerged for 24-hour ppa and 28-day continuous abstinence. Results from per protocol analyses (i.e., participants who completed all aspects of the study) corroborate the intent-to-treat findings. Conclusions: These results demonstrate that intensive, group CBT smoking cessation interventions are efficacious among African American smokers.

The effects of nicotine are seen in every trimester of pregnancy, from increased spontaneous abortions in the first trimester, to increased premature delivery rates and decreased birth weights in the final trimester. The birth weight of a baby is dependent on two factors: the gestational age of the fetus at the time of delivery and the rate of fetal growth. Nicotine has been shown to affect both of these factors. Carbon monoxide, also found in tobacco, forms carboxyhemoglobin, which inhibits the release of oxygen into fetal tissues. Nicotine readily gains access to the fetal compartment via the placenta, with fetal concentrations generally 15% higher than maternal levels. The primary metabolite of nicotine, cotinine, has a half-life of 15 to 20 hours and serum concentrations that are 10-fold higher than nicotine; thus, cotinlne provides a better index of nicotine exposure because of its longer half-life. Nicotine concentrates in fetal blood, amniotic fluid, and breastmilk. The fetus and neonate may also have environmental tobacco exposure that may be significant. In animal models and humans, nicotine increases maternal blood pressure and heart rate, with a concomitant reduction in uterine blood flow. An increase in fetal heart rate is also seen, which is thought to be caused by catecholamine release. The impact of nicotine on the respiratory and central nervous system is also reviewed. In conclusion, the physiological effect of tobacco on fetal growth seems to be a culmination of both the vasoconstricfive effects of nicotine on the uterine and potentially the umbilical artery and the effects on oxygenation by carboxyhemoglobin.

Summary. 2015 subjects were interviewed at musical events and raves in Northern Italy: average age 25.1, 42% female, 67% work, 42% study, 61% have higher certifi cate of education. 3.8% used drugs for the fi rst time in the last year, and 60% have been using drugs for over 5 years, age of fi rst use 16.3. In the last

The prevalence of last year use of alcohol, cigarettes, marijuana and cocaine in the U.S. population and conditional prevalence of a proxy measure of last year dependence among last year users of each drug class were assessed as a function of age, gender and ethnicity. Analyses were based on three aggregated waves (1991, 1992 and 1993) of the nationally representative samples of the general population aged 2 12 interviewed in the National Household Surveys on Drug Abuse (n = 87915). An approximation of DSM-IV drug-specific last year dependence for each drug class was derived from self-reported symptoms of dependence, data on frequency and quantity of use and drug-related problems reported for the last year. Descriptive and multivariate analyses were conducted. The inclusion of cigarettes among the drugs, the large number of cases and the wide age range of respondents ( 2 12) enable us to make drug, age, gender and ethnic comparisons not otherwise possible in any other data set. The proxy measure of dependence, however, has limitations. The five major findings are that: (1) nicotine is the most addictive of the four drugs we examined; (2) among female last year users of alcohol and marijuana, adolescents are significantly more at risk for dependence than any other age group of women; (3) conditional prevalences of last year dependence on alcohol, marijuana and cocaine are higher among adolescent females than adolescent males but significantly different only for cocaine; (4) among adults, the rates of dependence are higher among males than among females for alcohol and marijuana, but lower for nicotine; and (5) among last year users, whites are more likely than any other ethnic group to be dependent on nicotine and blacks to be dependent on cocaine.

Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in the production of other compounds. Various extracts from peppermint contain menthol as a major active constituent and have been used for centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome as well as an insect repellent. Menthol’s characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. Notwithstanding its plethora of benefits, menthol’s coldsensitivity response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in mentholated cigarette brands thus potentially leading to toxic effects. Menthol may prove a valuable lead structure for the synthesis of drugs that target multiple receptors involved with a number of pharmacological effects.

Abstract: Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for “complete” mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/ day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic- associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.

Dépendance tabagique ; Fumeurs invétérés ; Sevrage tabagique ; Envie compulsive ; Syndrome de sevrage Résumé Les spécialistes en tabacologie sont fréquemment confrontés à des fumeurs en grande difficulté pour s'arrêter de fumer, qu'ils soient motivés à le faire ou qu'ils y soient contraints pour des raisons sanitaires, économiques ou réglementaires. Ces fumeurs constituent une population hétérogène, mais ils ont en commun une forte dépendance au tabac et une importante consommation de cigarettes. Ils sont exposés aux conséquences morbides induites par leur incoercible tabagisme. Ils cumulent souvent d'autres facteurs défavorables à la réussite de la tentative de sevrage : troubles anxiodépressifs, co-consommations de substances psychoactives, précarité socioéconomique. Ils constituent une cible prioritaire des consultations spécialisées d'aide à l'arrêt du tabagisme. Ces dernières doivent optimiser et diversifier leurs propositions d'aide afin d'améliorer leurs interventions. Cette synthèse décrit ces consommateurs très dépendants en échec dans l'arrêt du tabagisme et présente les traitements médicamenteux et combinaisons thérapeutiques susceptibles d'aider le praticien dans la prise en charge de ces « fumeurs difficiles ».

The unconscious mind tends to disregard negations in its processing of semantic meaning. Therefore, messages containing negated concepts can ironically prime mental representations and evaluations that are opposite to those intended. We hypothesized that the subtle presentation of a negated concept (e.g., “no smoking”) would activate ironic motivational orientations as well. We tested this hypothesis in a public health context. Smokers viewed photographs in which no-smoking signs were either inconspicuously embedded (prime) or edited out (control). Primed smokers showed amplified automatic approach tendencies toward smoking-related stimuli, but not toward smoking-unrelated stimuli. Since passive priming effects generally serve to facilitate forms of action, not inhibit them, anti-smoking and other public health campaigns may ironically increase the very behaviors they seek to reduce.

With an increasing population experiencing tobacco dependence, an enormous public health medical cost has been induced due to first-hand, secondhand , and third-hand smoking. A variety of instruments are available to aid in smoking cessation, including standard and adjunct therapies, for which acupuncture constitutes a safe and economic measure. Offering an overview of this traditional Chinese medicine practice, this literature review analyses 27 clinical studies, covering 15,794 participants aged 15-84 years old from Africa, Asia, Europe and North America. The outcomes reveal the effectiveness of acupuncture in minimising cigarette cravings, tobacco consumption, and nicotine dependence, through either a single employment of this method or a combined treatment method. Suggestions for research and practical implications to improve the usefulness of acupuncture in dealing with smoking-related health are given.

Individuals are different 'chronotypes' with early 'larks' and late 'owls' forming the limits of a normal distribution in the population. We recently described that late chronotypes who suffer from a conflict between internal and external time ('social jetlag') suffer from more mental distress and are more likely to smoke than early chronotypes (Wittmann, Dinich, Merrow, and Roenneberg, 2006. Social jetlag: mis-alignment of biological and social time. Chronobiology International, 23:497-509.). We performed a detailed analysis of the same database collected in 2002 comprising 134 daily smokers and 366 nonsmokers, scrutinizing the relationships between chronotype, smoking, and alcohol consumption as well as psychological well-being using a multiple mediation analysis. On average, smokers tend to be later chronotypes, report more sleep-associated psychosomatic symptoms, are more depressed, less balanced, and less vigilant. The mediation analysis suggests that only those late chronotypes who smoke and those who drink more suffer from increased psychological distress. We suggest that 'chronotype' is introduced as an additional factor in substance use, that is, when considering motives for smoking and drinking.

Craving to smoke is often conceptualized and measured as a tonic, slowly changing state induced by abstinence. In this article, we review the literature on the existence, causes, and treatment of cue-induced cravings: intense, episodic cravings typically provoked by situational cues associated with drug use. In laboratory research, smokers exposed to smoking-related cues demonstrate increased craving as well as distinct patterns of brain activation. Observational field studies indicate that such cue-induced cravings are substantially responsible for relapse to smoking but that smoking can often be averted by coping responses. The effects of pharmacological interventions are mixed. Steady-state medications (bupropion, varenicline, nicotine patch) do not appear to protect smokers from cue-induced cravings. However, acutely administered nicotine medications (such as nicotine gum and lozenge), used after cue exposure as "rescue medications," can help a smoker's recovery from cue-induced cravings. Cue-induced craving plays an important role in smoking and relapse and likely in other addictions as well. Treatments to mitigate the effect of cue-induced craving are both important and needed.

Cigarette smoking represents the most important source of preventable morbidity and premature mortality worldwide. Approximately 100 million deaths were caused by tobacco use in the 20th century. There are Ͼ 1 billion smokers worldwide, and globally the use of tobacco products is increasing, with the epidemic shifting to the developing world. Tobacco dependence is a chronic condition that often requires repeated intervention for success. Just informing a patient about health risks, although necessary, is usually not suffi cient for a decision to change.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Objectives: Most of the addiction studies focus on very specific aspects of addictions , often with contradictory results, and integrated studies are quite rare. Experimental studies comparing underlying mechanisms of addictions and analyzing data from an integrative psychological and genetic perspective are almost nonexistent. The aim of the present paper is to describe the research protocol of the Psychological and Genetic Factors of Addictive Behaviors (PGA) study, which applies an integrative approach to understanding the acquisition, development, and maintenance of addic-tive behaviors. Methods: A wide-spectrum national study was carried out. Data were collected from 3,003 adolescents. Addictions to both psychoactive substances and behaviors were thoroughly assessed via psychometrically robust scales, which also included assessment related to a wide range of related psychological dimensions. Additionally, a DNA sample was also collected from participants. Results: The paper presents the detailed methodology of the PGA study. Data collection procedures, instrumentation, and the analytical approach used to attain the research objectives are described. Conclusions: Future plans, along with potential contributions of the PGA study, are also discussed. It is envisaged that the study will provide a unique opportunity to test possible mechanisms and causal pathways mediating the associations of genetic factors , psychological characteristics, and addictions.

An emerging approach in the addiction literature is to use neuroscientific data to predict addiction-related outcomes (e.g., relapse). Studies using this approach are grounded in process-level models of addiction, and thus leverage neuroscientific knowledge and methods about those presumptive processes to gain explanatory power that would otherwise remain elusive. For example, neural activation during basic inhibitory control and conflict resolution tasks predicts success and failure during attempts to quit smoking and drinking alcohol, above and beyond task performance and other standard measures of risk. In this chapter, I review studies that use functional neuroimaging to predict outcomes related to nicotine, alcohol, and drug use as well as food intake. I also identify several conceptual considerations in using the approach and directions for its future growth.

Objective Electronic Nicotine Delivery Systems (ENDS) have recently been attracting interest for their potential as a less harmful alternative to smoking, their rising popularity and the regulatory issues they raise. The news media can play an important role in shaping public perceptions of new technologies. It is, therefore, important to understand the ways the news media present ENDS. This paper examines how ENDS are represented in the UK and in the Scottish press. Methods Twelve national UK and Scottish newspapers and the three most popular online news sources were searched between 2007 and 2012. A thematic analysis was conducted to explore how the meanings, uses and users of ENDS are presented, and whether and how this has changed. Results Newspaper coverage of ENDS increased substantially over this period. Five key themes emerged from the analysis: getting around smokefree legislation; risk and uncertainty; healthier choice; celebrity use; price. Conclusions Drawing on the diffusion of innovations theory, we suggest that newspaper constructions of ENDS provide readers with important information about what ENDS are for, how they work, and their relative advantages. These themes, and dominance of more positive meanings, raise a number of issues for tobacco control, including concerns around celebrity use and promotion; the impact of increasing ENDS use on social norms around smoking; their potential to undermine smokefree legislation; and their promotion as effective cessation aids.

Parkinson's disease (PD) affects one in every 100 persons above the age of 65 years, making it the second most common neurodegenerative disease after Alzheimer's disease. PD is a disease of the central nervous system that leads to severe difficulties with body motions. The currently available therapies aim to improve the functional capacity of the patient for as long as possible; however they do not modify the progression of the neurodegenerative process. The need for newer and more effective agents is consequently receiving a great deal of attention and consequently being subjected to extensive research. This review concisely compiles the limitations of currently available therapies and the most recent research regarding neuroprotective agents, antioxidants, stem cell research, vaccines and various surgical techniques available and being developed for the management of PD. #

Rationale
Human and animal studies over the last two decades report that nicotine can improve cognitive performance. Prospective memory (PM), the retrieval and implementation of a previously encoded intention, is also improved by pre-administration of nicotine. As with other nicotine effects, however, predicting precisely how and when nicotine improves the processes engaged by PM has proved less straightforward.
Objective
We present two studies that explore the source of nicotine’s enhancement of PM. Experiment 1 tests for effects of nicotine on preparatory attention (PA) for PM target detection. Experiment 2 asks whether nicotine enhances processing of the perceptual attributes of the PM targets.
Materials and methods
Young adult non-smokers matched on baseline performance measures received either 1 mg nicotine or matched placebo via nasal spray. Volunteers completed novel PM tasks at 15 min post-administration.
Results
Experiment 1 confirmed that pre-administration of nicotine to non-smokers improved detection rate for prospective memory targets presented during an attention-demanding ongoing task. There was no relationship between PM performance and measures of preparatory attention. In experiment 2, salient targets were more likely to be detected than non-salient targets, but nicotine did not confer any additional advantage to salient targets.
Conclusion
The present study suggests that nicotinic stimulation does not work to enhance perceptual salience of target stimuli (experiment 2), nor does it work through better deployment of preparatory working attention (experiment 1). An alternative explanation that nicotine promotes PM detection by facilitating disengagement from the ongoing task is suggested as a future line of investigation.

Background: Scholastic works suggest that those at risk for exercise addiction are also often addicted to illicit drugs, nicotine, and/or alcohol, but empirical evidence is lacking. Aims: The aim of the present work was to examine the co-occurrence of illicit drug, nicotine, and alcohol use frequency (prevalence of users) and severity (level of problem in users) among exercisers classified at three levels of risk for exercise addiction: (i) asymptomatic, (ii) symptomatic, and (iii) at-risk. Methods: A sample of 538 regular exercisers were surveyed via the Qualtrics research platform. They completed the (i) Drug Use Disorder Identification Test, (ii) Fagerström Test for Nicotine Dependence, (iii) Alcohol Use Disorder Identification Test, and (iv) Exercise Addition Inventory. Results: A large proportion (n = 59; 10.97%) of the sample was found to be at risk for exercise addiction. The proportion of drug and alcohol users among these participants did not differ from the rest of the sample. However, the incidence of nicotine consumption was lowest among them. The severity of problematic substance use did not differ across the groups. Conclusions: These findings suggest that substance addiction and the risk for exercise addiction are unrelated. In fact, those at risk for exercise addiction exhibited the healthiest profile related to the prevalence of smoking.

Several ancient Mayan vessels from the Kislak Collection of the US Library of Congress were examined for the presence of alkaloids. One of them, a codex-style flask, bears a text that appears to read yo-'OTOT-ti 'u-MAY, spelling y-otoot 'u-may 'the home of its/his/her tobacco'. Samples extracted from this Late Classic period (600 to 900 AD) container were analyzed by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) methods. Nicotine was identified as the major component of the extracts. LC/MS analyses also yielded signals due to nicotine mono-oxides. The identities of the compounds were determined by comparison of the chromatographic and/ or mass spectral characteristics with those from standards and literature data. High-resolution high mass accuracy tandem mass spectrometry (MS/MS) spectra of protonated nicotine and nicotine mono-oxides were measured to verify and to correct previous product ion assignments. These analyses provided positive evidence for nicotine from a Mayan vessel, indicating it as a likely holder of tobacco leafs. The result of this investigation is the first physical evidence of tobacco from a Mayan container, and only the second example where the vessel content recorded in a Mayan hieroglyphic text has been confirmed directly by chromatography/mass spectrometry trace analysis.

Emesis, also known as nausea and vomiting, are common symptoms associated with ingestion of toxicants, drug side effects, advanced terminal diseases such as cancer and postoperative procedures. Emesis is mediated through the coordinated
action of central and peripheral regulatory centres that involve receptors including dopamine Type 2, serotonin, muscarinic cholinergic, histamine, cannabinoids and NK-1 receptors. Many anti-emetic drugs targeting these receptors are currently in
use but they also cause undesirable side effects such as excessive sedation, hypotension,dry mouth, dysphoria, hallucinations and extrapyramidal signs. This review highlights the pharmacological mechanism of emesis and current antiemtic drugs
together with detailed analysis of in vitro and in vivo anti-emetic bioassay models. The pharmacology of crude natural products extracts and purified anti-emeticcompounds (cannabinoids, chalcones, diarylheptanoids, flavonoids, hydroxycinnamic
acids, lignans, phenylpropanoids, polysaccharides, saponins, terpenes and glycosidic derivatives) are also systematically presented with their mechanism of action. The potential of natural products as sources of new clinically proven anti-emetic drugs are discussed.

Background: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. Objectives: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. Methods: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. Results: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16–57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. Conclusion: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for "complete" mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

Nicotine patches in Alzheimer's disease: Pilot study on learning, memory, and s4fety. PHARMACOL BIOCHEM BEHAV 51(2/3) 509-S 14, 1995. -In view of the cholinergic deficits present in patients with Alzheimer's disease (AD), a widely investigated treatment strategy for the cognitive deficits in AD is cholinergic stimulation. Although nicotinic choline& receptor binding has been demonstrated to be deficient in the AD brain, the predominant theoretical and therapeutic focus to date has been on muscarinic choline&c receptors and systems. The purpose of the present study was to evaluate the effects of sustained nicotine administration on behavior, cognition, and physiology. A double-blind placebo-controlled trial was conducted in which six patients with probable AD were exposed to 7,8, and 7 days of placebo, nicotine, and washout, respectively. Daily sessions evaluating kaming, memory, and behavior were conducted. Global cognitive functioning, rest and activity levels, cardiac activity, and blood levels were also measured. Findings included improved learning during the nicotine condition, which persisted throughout washout. Memory, behavior, and global cognition were not significantly affected. Sustained administration of nicotine appeared to be safe, although sleep showed a significant decrease.

Argentina and Uruguay are among the countries in which a large proportion of young women smoke. The rate of smokers during pregnancy in both countries is not well known, and data on the characteristics of women who quit smoking during pregnancy compared to those who continue smoking are not available. We conducted a survey including 1512 pregnant women > or = 18 years old (796 in Argentina; 716 in Uruguay), during antenatal visits in public hospitals of large urban regions; 44% of the women in Argentina and 53% in Uruguay had been or were regular smokers. 11% of the surveyed women in Argentina and 18% in Uruguay continued smoking during pregnancy. In both countries, the proportion of women who lived with smokers, allowed smoking at home, and were regularly or always exposed to tobacco smoke indoors, were 49%, 46% and 20% in the subgroup of women who never smoked, 67%, 60% and 32% in those who quit, and 78%, 75% and 52% in those who continued smoking, respectively. The study confi...

In the first study to examine direct nicotinic augmentation of central cholinergic functioning in Alzheimer's disease, six patients were studied in an intensive pilot study with three doses (0.125, 0.25, and 0.5 μg/kg/min) of intravenous nicotine and placebo. Cognitive tests showed a decrease in intrusion errors on the middle (0.25 μg) dose. Prominent behavioral effects were noted, with significant dose-related increases in anxiety and depressive affect. These results suggest that central nicotinic cholinergic stimulation deserves further investigation as a treatment in Alzheimer's disease and that nicotine may also be a useful investigative tool in other populations as a probe of central cholinergic function, especially in regard to the modulation of affect.

Rationale This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure. Objectives This review capitalizes on the authors’ collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models. Results Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses. Conclusions The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose–response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.

The authors sought to further validate a cigarette purchase task (CPT), a self-report analogue of a progressive-ratio operant schedule, for the assessment of the relative reinforcing efficacy (RRE) of nicotine in smokers. The measure was assessed in terms of its correspondence to typically observed operant behavior, convergent validity, and divergent validity. Participants were 33 individuals (58% male, age M ϭ 19.30 years) who smoked at least weekly (M ϭ 5.31 cigarettes/day) and underwent a single assessment session. Data from the CPT exhibited the predicted inverse relationship between consumption and price, the predicted relationship between consumption and expenditure, and a heterogeneous pattern of interrelationships among the indices of reinforcement. In addition, 2 indices from the measure, intensity of demand and maximum expenditure for cigarettes, exhibited robust convergent and divergent validity. Although this is an incipient research area and the current study used a relatively small sample, these findings support the validity of a CPT as a time-and cost-efficient method for assessing nicotine reinforcement. Theoretical implications of the findings, limitations, and future directions are also discussed.

Traditional cue reactivity provides a methodology for examining drug triggers and stimuli in laboratory and clinical settings. However, current techniques lack standardization and generalization across research settings. Improved methodologies using virtual reality (VR) cue reactivity extend previous research standardizing exposure to stimuli and exploring reactions to drug cues in a controlled VR setting. In a controlled pilot trial, 13 nicotine-dependent participants were allowed to smoke ad libitum then exposed to VR smoking and VR neutral cues and compared on craving intensity. VR smoking cues significantly increased craving compared to VR neutral cues. On average, craving intensity increased 118% during exposure to VR smoking cues. Implications for substance abuse research and treatment using VR to assess cessation and anticraving medications are discussed. D

Objective: The leaves of sage (Salvia officinalis L., Lamiaceae) are reported to have a wide range of biological activities, such as anti-bacterial, fungistatic, virustatic, astringent, eupeptic and antihydrotic effects. To determine the mnemogenic effect of sage leaves, we investigated the effects of ethanolic extract of sage leaves and its interaction with cholinergic system on memory retention of passive avoidance learning in rats. Methods: Post-training intracerebroventricular (i.c.v) injections were carried out in all the experiments except ethanolic extract (i.p. intraperitoneally). Results: Administration of ethanolic extract (50 mg/kg), pilocarpine (0.5 and 1 mg/rat), the muscarinic cholinoceptor agonist, and nicotine (0.1 and 1 g/rat) increased, while mecamylamine (1, 5 g/rat), the muscarinic cholinoceptor antagonist, and mecamylamine (0.01 and 0.1 g/rat), the nicotine cholinoceptor antagonist decreased memory retention in rats. Activation of muscarinic cholinoceptors by pilocarpine potentiated the response of ethanolic extract. Also, pharmacological blockade of scopolamine attenuated potentiating effect of ethanolic extract. Activation of nicotinic cholinoceptor by nicotine potentiated the response of ethanolic extract. Blockade of nicotinic cholinoceptor by mecamylamine attenuated the response of ethanolic extract. Conclusion: It is concluded that the ethanolic extract of salvia officinalis potentiated memory retention and also it has an interaction with muscarinic and nicotinic cholinergic systems that is involved in the memory retention process.

Introduction: Genetic variants within nicotinic receptors have been shown to modulate an individual’s risk for nicotine dependence. Among the most reproducible risk factor is a non-synonymous polymorphism (rs16969968) within the alpha5 nicotinic receptor subunit gene, CHRNA5. Genetic factors also contribute to CHRNA5 mRNA expression and risk for substance abuse, but the specific variants responsible for changes in mRNA expression are unclear. Methodology: To determine the presence of cis-acting functional genetic variants contributing to CHRNA5 mRNA expression, we measured allelic expression of CHRNA5 within post-mortem human prefrontal cortex brain tissue. Using allelic expression as a phenotype, we scanned the CHRNA5 gene locus for polymorphisms responsible for imbalanced allelic expression. Polymorphisms determined to be responsible for allelic expression were genotyped in our full brain cohort and total CHRNA5 expression was compared across genotype using quantitative PCR. We then tested these expression-related variants for clinical association with nicotine dependence. Results: We uncovered a functional genetic locus 13.5kb upstream of CHRNA5 acting as an enhancer of CHRNA5 mRNA expression. Minor allele carriers for enhancer variants displayed >2- fold differences in allelic expression, while individuals homozygous for the enhancer minor alleles expressed >4-fold more cortical CHRNA5 mRNA. Haplotype structure analysis predicts that the enhancer SNPs rarely occur on the same allele as the previously implicated non-synonymous variant. Taking into account this relationship, enhancer region SNPs confer significant risk only when you control for the presence of the non-synonymous variant in a joint SNP analysis. Conclusions: Polymorphisms within a transcriptional enhancer located 13.5kb upstream of CHRNA5 modulate CHRNA5 mRNA transcription. These enhancer variants confer risk for nicotine dependence in a context-dependent manner. Understanding the biological functions of these clinically relevant genetic variants revealed a SNP-SNP interaction increasing risk for nicotine dependence that is otherwise obscured by haplotype structure when using traditional clinical association methods. These findings aid in the construction of complex biological or genetic models of nicotine dependence that mimic human factors. The relevance of the enhancer CHRNA5 polymorphism in other brain regions and peripheral tissues (e.g., the lung) needs further study. Moreover, identification of functional CHRNA5 variants facilitates the analysis of gene-gene interactions with respect to nicotine and other drug addictions.

"Chemical analysis of residue extracted from stone pipes and pipe fragments excavated at sites in the southern Pacific Northwest Coast of North America demonstrate that hunter-gatherers smoked the psychostimulant tobacco (Nicotiana sp.) by at least AD 860. Non-farming ethno-historic Native Americans throughout the west gathered and sometimes cultivated tobacco for ritual and religious purposes, but until now the antiquity of the practice on this part of the continent was unknown. Method validation includes chemical characterization of a suite of smoke plants and experimental reproduction of “smoked” pipe chemistry; Results indicate biomarkers are traceable for several species commonly smoked by ethnographic native peoples, including tobacco (nicotine, cotinine), tree tobacco (anabasine), and kinnikinnick (arbutin). Developed methods—where residue is extracted directly from the stone or clay matrix of whole and fragmentary archaeological pipes—may be applied in similar studies investigating the spread and use of ritual smoke plants in the ancient Americas and elsewhere.

Background Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than nonsmokers. Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement.

Recent advances in studies of nicotinic agents in humans have begun to more carefully define cognitive operations that can be influenced by nicotinic stimulation and/or blockade. Careful separation of the cognitive domains affected by nicotinic stimulation has identified attentional performance as the most likely candidate to be positively influenced by nicotinic receptor activation. Studies of the effects of nicotinic systems and/or nicotinic receptor stimulation in pathological disease states such as Alzheimer's disease, Parkinson's disease, attention deficit/ hyperactivity disorder and schizophrenia show the potential for therapeutic utility of nicotinic drugs. In contrast to studies in pathological states, studies of nicotine in normal-non-smokers tend to show deleterious effects. This contradiction can be resolved by consideration of cognitive and biological baseline dependency differences between study populations in terms of the relationship of optimal cognitive performance to nicotinic receptor activity. Although normal individuals are unlikely to show cognitive benefits after nicotinic stimulation except under extreme task conditions, individuals with a variety of disease states can benefit from nicotinic drugs. Attentional function/ dysfunction may serve as an endophenotypic therapeutic target for nicotinic drug development.

Pharmacological cognitive enhancement refers to improvement in cognitive functions after drug use in healthy individuals. This popular topic attracts attention both from the general public and the scientific community. The objective was to explore innovative mechanisms of psychostimulant's action, whose potential effectiveness was assessed in randomized placebo-controlled trials (RCTs). A systematic review was carried out, using the words "attention", "memory", "learning", "executive functions", and "vigilance/ wakefulness" combined to "cognitive enhancer" or "smart drug". Methylphenidate, amphetamines, modafinil, nicotine, acetylcholine esterase inhibitors and antidepressants were extensively studied in previous meta-analyses and were not included in the present work. Drugs were classified according to their primary mode of action, namely catecholaminergic drugs (tolcapone, pramipexole, guanfacine), cholinergic drugs (anticholinergics), glutamatergic drugs (ampakines), histaminergic drugs, and nonspecified (glucocorticoids). Overall, 50 RCTs were included in the present review. In conclusion, a number of new active drugs were found to improve some cognitive functions, in particular verbal episodic memory. However the number of RCTs was limited, and most of the studies found negative results. Future studies should assess both effectiveness and tolerance of repeated doses administration, and individual variability in dose response (including baseline characteristics and potential genetic polymorphisms). One explanation for the limited number of recent RCTs with new psychostimulants seems to be the ethical debate surrounding pharmaceutical cognitive enhancement in healthy subjects.