Writer #11 Writer #11 has an MS in Health Science / Behavioral Health Counseling as well as an EdD focusing on health and wellness education with a focus on changing behaviors around drugs, alcohol and smoking. Writer #11 has extensive experience as a counselor and administrator in a variety of health related institutions including Department of Psychiatry and Health Behavior at the Medical College of Georgia Health System and Department of Medicine, University of Florida Health Science Center. This writer currently has a private practice as a Behavioral Health and Education consultant focusing on recovery, family intervention, recovery and life coaching. Writing Sample: Smoking Treatment
Cigarette smoking is the single most preventable cause of death in the United States. Major gains have been made in reducing smoking prevalence over the past three decades. Overall, smoking has dropped from 51% of the US population in the late 1940’s to 24%. At the same time, nicotine remains the most widely used and abused drug in the United States and world. There are approximately 1 billion cigarette smokers in the world today and approximately 3 million people die each year from smoking related illnesses. Most tobacco-dependent persons never achieve lasting abstinence and half die prematurely of tobacco related disease. In the United States less than 10 per cent of the nearly 20 million people who quit smoking for a day remain abstinent one year later. With only 2 to 3 per cent of smokers succeeding in smoking cessation, smoking cigarettes is considered among the most addicting drugs. One third of occasional cigarette smokers graduate to physical dependence. Both cigarette smoking and exposure to environmental tobacco smoke (ETS) have a major impact on publichealth. Recent data reporting urinary cotinine measurement as evidence of tobacco exposure from 602 elementary school children provides important preliminary evidence of the relevance of environmental exposure and suggests that the most exposure occurs among the poorest children1. Of the estimated 480,000 smoking related deaths in the United States, 53,000 have been attributed to ETS making it the third leading cause of preventable death after active smoking and alcohol use. Exposure to ETS is virtually non-existent in the patient’s medical history or database. Unfortunately, it is rarely an area of medical specialty, treated as seriously as diabetes or alcoholism or depression, or considered a medical emergency in need of intervention and effective treatment and relapse prevention.
EPIDEMIOLOGICAL PATTERNS AND CHANGE:
Cigarette smoking in the United States increased rapidly in the 1930s and 1940s. 2Smoking prevalence peaks between the ages of 20 and 40. Smoking prevalence is higher among males than among females and higher among blacks than among whites. Twenty four percent of Americans over the age of 18 are currently smoking. In the 1950s the first reports of the health effects of cigarette smoking appeared and the increases in tobacco consumption were slowed down by a number of reports linking smoking to disease. Starting in 1973, the year that tobacco ads were banned from television, cigarette consumption per capita has decreased steadily. In 1994, it was at the same level as in 1942. Unfortunately, the news regarding teen smoking is not encouraging. Smoking among middle and high school students has risen steadily since 1992.
The dramatic decline in smoking prevalence among adults is largely attributed to increased public awareness of the dangers of cigarettes and subsequent social and political intervention. Among adults, it is no longer fashionable, sophisticated or socially rewarding to be a smoker. This change in public perception and attitude has made the arguments for addictive disease more compelling because social reinforcement as a determinant for smoking has become a moot point among adults. Smokers continue to smoke in spite of harmful physical and social consequences because they are addicted.
Survey data released by The Centers for Disease Control and Prevention confirms this position. In a report released in December 1997, the CDC3 reported that 70 percent of current smoker’s want to quit but cannot. The good news is that our educational efforts have had a positive impact on adult perception and attitudes about smoking. The bad news is that we lack the medical and psychological sophistication to intervene effectively and aggressively treat those who want to quit4.
Nicotine is a tertiary amine consisting of a pyridine and a pyrrolidine ring. Nicotine binds stereoselectively to nicotinic cholinergic receptors throughout the brain. with greatest binding sites found in thecortex, thalamus, interpeduncular nucleus, amygdala, septum, locus coeruleus, and brain stem motor neurons . Nicotine activates acetylcholine receptors, many of which are located presynaptically on dopaminergic projections from the ventral tegmental area to the nucleus accumbens. Nicotine is metabolized extensively primarily in the liver to cotinine. Cotinine is then metabolized to 3-hydroxycotinine the most abundantnicotine metabolite found in the urine.The action of inhaled nicotine results in the rapid releaseof dopamine into the synaptic cleft as measured by in vivo microdialysis with increased outflow in the nucleus accumbens. Just looking at a cigarette, lighting a match or watching an approaching cigarette to smoke would be expected to increase dopamine outflow in anticipation of reward. The effects of dopamine overflow in the nucleus accumbens are similar to other drugs of abuse .
Smoking does not interfere with work and in general has a limited effect on observable
behavior. This may result from nicotinic receptors shutting down shortly after nicotine binding, thus limiting the duration of mesolimbic dopamine stimulation. This would result in a shorter-lived euphoria followed by a gradual decline until the next bolus of nicotine reaches the brain to "switch-on" nicotinic receptors and repeat the pleasure signal once again. Consequently, addicted smokers eventually up-regulate nicotinic cholinergic receptors to help compensate for this action. CIGARETTE SMOKING ADDICTION:
Like all drugs of abuse, nicotine is highly rewarding. Freely moving animals avidly self-administer nicotine intravenously. Nicotine, like cocaine, ethanol, amphetamine and opiates have been shown to stimulate dopamine release in the nucleus accumbens, which is the biological marker of the brains reward system and the primary target for all drugs of abuse.
Smoking is the most efficient way to administer nicotine to the brain. Inhaled nicotine reaches the brain within 10 seconds where it stimulates extracellular dopamine release along the mesolimbic dopamine system creating in the smoker a feeling of wellbeing and satisfaction. The increase in synaptic dopamine sends a pleasure signal over and over again, which the smoker desires to repeat. This forms the biological basis for drug reward and addiction.
Once dopamine clears the synapse, this complex pleasure circuitry is in a state of imbalance and craving and withdrawal occur. The brain is sending signals that it needs more dopamine. The smoker interprets this message as “I need another cigarette.” Drug craving involves dopamine depletion that is often triggered by exogenous cues and ritualistic behavior.
No one smokes for effects on the lung, or to have a hoarse voice or smelly clothes. Smoking cigarettes causes a characteristic addictive illness with purposeful, goal-directed behavior aimed at the acquisition and use of cigarettes. Smoking continues despite consequences and the realization of health risks and is characterized by a narrowing of interests and preoccupation with smoking.
Relapse is the rule as neuroadaptational changes re-define normal brain function. As the addiction progresses, the smoker has a characteristic narrowing of interests and increase in identification as a “smoker”. Tobacco use creates a new level of brain reward or pleasure that becomes defined as normal and any attempt to reduce this stimulation through tobacco abstinence leads to a decreased level of pleasure or anhedonia. Thus, it is abnormal for the user to abstain from the drug once neuroadaptive changes have occurred.
Prolonged abstinence in addicted smoker’s cause an up-regulation of noradrenergic receptors throughout the brain causing withdrawal syndrome to occur. Symptoms include restlessness, anxiety, agitation, insomnia, depressed mood, dysphoria, inability to concentrate and mood swings. Moreover, dopamine changes may cause hyperphagia, anhedonia, boredom, and drug cravings.
When another cigarette is smoked, the brain achieves short-lived, nicotine induced state of homeostasis. Simply put, when they smoke they feel better--when they do not smoke the feel bad.
High rates of relapse are common for cigarette smokers5. One factor in relapse is acute re-exposure to tobacco after a period of abstinence. The more passage of time, duration of abstinence, the less effect that nicotine re-exposure has on the previously addicted.
Tobacco Smoking & Depression: Tobacco Smoking & Depression: Smoking cessation is often accompanied by dysphoria and sometimes by depression. Some smokers may have been depressed in the past but for others years of smoking appears to put them at risk for withdrawal depression. Do people with a personal or family history of depression, enjoy smoking or get attached to smoking more than others? Recent studies have confirmed that lifetime prevalence of major depression is more common among smokers than nonsmokers, 6.6 vs. 2.9%. Epidemiological Catchment Area (ECA) analysis of 3,000 individuals also demonstrated that smokers with a lifetime history of major depression were less likely to succeed in smoking cessation compared to smokers without depression 14 to 28%6.These findings have been confirmed by many other investigators and in a large number of studies ,
Anecdotally, clinicians have long noted the emergence of a sub-group of smokers that appear to self medicate depressive and other psychiatric symptoms. While nicotine is the primary psychoactive constituent in tobacco smoke numerous other chemicals also appear to have psychoactiveand antidepressant properties .
Recent data utilizing positron emission technology has demonstrated thata non-nicotine constituent of cigarette smoke induces changes in brainMAO activity, suggesting that smokers are getting significantanti-depressant effects from smoking. Researchers at Brookhaven NationalLaboratory have recently produced images showing 30-40 percent decreasesof MAOb in the brains of smokers, compared to nonsmokers.
MAO exists as MAOa and MAOb subtypes that are different gene products. In the brain MAOa oxidizes serotonin and norepinephrine in catecholamineneurons and MAOb oxidizes serotonin. Both forms oxidize dopamine. MAObis reduced in smokers compared to nonsmokers and former smokers. It islikely that MAOa and MAOb inhibition by tobacco smoke contributes to thehigh rates of relapse among smokers15. These data help explain theresistance to treatment and multiple treatment failures among smokers. Other forms of nicotine delivery, like the patch and the gum are seldom,if ever abused and do not appear to have antidepressant effects.
Recent studies have confirmed that lifetime prevalence of major depression is more common among smokers than nonsmokers, 6.6 vs. 2.9%. Conducted in the
Epidemiological Catchment Area (ECA) of St. Louis, this study of 3,000 individuals also demonstrated that smokers with a lifetime history of major depression were less likely to succeed in smoking cessation compared to smokers without These findings have been confirmed by many other investigators and in a large number of studies7,8.
Anecdotally, clinicians have long noted the emergence of a sub-group of smokers that appear to self medicate depressive and other psychiatric symptoms. While nicotine is the primary psychoactive constituent in tobacco smoke numerous other chemicals also appear to have psychoactive and antidepressant properties91011.
Recent data utilizing positron emission technology has demonstrated that a non-nicotine constituent of cigarette smoke induces changes in brain MAO activity, suggesting that smokers are getting significant anti-depressant effects from smoking. Researchers at Brookhaven National Laboratory have recently produced images showing 30-40 percent decreases of MAOb in the brains of smokers, compared to nonsmokers.
MAO exists as MAOa and MAOb subtypes that are different gene products. In the brain MAOa oxidizes serotonin and norepinephrine in catecholamine neurons and MAOb oxidizes serotonin. Both forms oxidize dopamine. MAOb is reduced in smokers compared to nonsmokers and former smokers. It is likely that MAOa and MAOb inhibition by tobacco smoke contributes to the high rates of relapse among smokers10. These data help explain the resistance to treatment and multiple treatment failures among smokers. Other forms of nicotine delivery, like the patch and the gum are seldom, if ever abused and do not appear to have antidepressant effects. Withdrawal Nicotine’s effect on the brain, via cigarette smoking is the primary cause of dysphoric mood states observed during nicotine withdrawal. Depressive symptoms are more common among those who have family histories or personal histories of depression, and more resistant to treatment. Depression is associated with increased prevalence of smoking. Depression and dysphoric mood-prone individuals are more likely to experience increased dysphoric mood when they quit smoking. Administering a depression inventory such as the Beck or Zung is highly recommended at the onset of smoking cessation treatment because depressive states are predictive of smoking relapse9.
Given our increasing knowledge about the addictive nature of smoking, new and effective treatments should become available which enable physicians to go far beyond simple detoxification to also treat the addiction12. Drug addiction is a brain disease and new treatments are being tested which help prevent relapse, reverse changes induced by the drugs, and even prevent re-intoxication. The application of these new treatments requires a re-education of treatment professionals so that patients with addiction can benefit from combined treatment in the same way that depressed patients are treated--medications plus therapy is better than either alone. The most recent research in this area involves relapse, dopamine and relapse prevention treatment with Bupropion HCL-SR (Zyban).
Smoking is the most common addiction and the most common failure. Prevention of smoking is a major public health goal since smoking is so addicting and an extremely difficult addiction to treat. With only 2 to 3 per cent of smokers succeeding in cessation attempts, smoking cigarettes is considered among the most addicting drugs. High rates of relapse are common for cigarette smokers 5. Patients explain that they tried this or that nicotine detoxification and consider it a treatment failure. Many patients and their families have lost hope and resigned themselves to lives of smoking consequences. The failure in smoking cessation has suggested to many Americans that addiction treatment is unsuccessful. Alcoholism treatment success is approximately 50%, opioid dependence is 60%, cocaine dependence is 55% and nicotine dependence is 30%13. Nicotine is the addicting drug that has the poorest success rate with only 20-30% not returning to smoking at 12 months after treatment.
Smoking cessation starts with the person asking for treatment or the health care provider helping the person see that cessation is inevitable and necessary. Diagnosis is the first step. Many patients deny use of tobacco products and when there is evidence on clinical examination the physician can tell the patient that a simple urine test can detect use.
THE DIAGNOSIS BY THE DSM IV?
The DSM IV considers cigarette smokers as equivalent to nicotine dependence. Nicotinewithdrawal shares many features with alcohol and opiate withdrawal and is list of target symptoms used to titrate nicotine detoxification treatments. Diagnostic criteria for 292.0 Nicotine Withdrawal A.
Daily use of nicotine for at least several weeks.
Abrupt cessation of nicotine use, or reduction in the amount of nicotine used, followed within 24 hours by four (or more) of the following signs:
The symptoms in Criterion B cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning. D.
The symptoms are not due to a general medical condition and are not better
accounted for by another mental disorder DSM IV.
Unfortunately, the DSM IV does not include urine or serum cotinine in the diagnosis of intoxication and the absence of nicotine metabolic products in the confirmation of abstinence. Furthermore, cigarette smoke and not nicotine per se is the dependence in question.
SMOKING CESSATION: General Issues
Physicians who provide primary care have an excellent opportunity to encourage addicted patients to quit and promoting prevention among patients before addiction. Physicians can accomplish a good deal with a short time devoted to smoking. Minimal contact physician counseling can cause cessation rates of up to five percent14. Such medical contact by physicians who have smoking rates of approximately 3% as a group can be extremely effective. Physicians should add smoking status (current, former, never) should be added to other vital signs (blood pressure, pulse, temperature, and respiratory rate) documented at each visit or patient contact.
Use or dependence on other drugs or alcohol.
Which cigarette would they least like to give up, i.e. after meal, wake up?
Quitting experience, previous withdrawal symptoms.
Interest in quitting. Why? Who wants them to quit?
Obstacles to quitting. Long term and short term.
Of those smokers who successfully quit, less than 25% quit on their first attempt. Most individuals who smoke have 3-4 failures before they stop smoking for good. In the United States, about 45% of those who have ever smoked eventually stop smoking. Although over 80% of individuals who smoke express a desire to stop smoking and 35% try to stop each year, less than 5% are successful in unaided attempts to quit. Nicotine replacement therapy is effective in 13% of smokers15. A recent meta-analysis on the efficacy of nicotine replacement therapies in smoking cessation examined nearly 18,000 subjects from all randomized trials of nicotine gum, patches, sprays and inhalers. This study has strongly suggested that all of the currently available forms of nicotine replacement are more effective therapies than “cold turkey” to aid smoking cessation. In individuals who smoke cigarettes, heart rate decreases by 5 to 12 beats per minute in the first few days after stopping smoking, and weight increases an average of 2-3 kg over the first year after stopping smoking. Mild symptoms of withdrawal may occur after switching to low-tar/nicotine cigarettes and after stopping the use of smokeless (chewing) tobacco, nicotine gum, or nicotine patches. The current treatment of cigarette smokers (and even the DSM IV diagnosis of nicotine dependence) gives the false
impression that nicotine is the major or only problem the smoker has and it would therefore follow that treatment with nicotine would be effective. This is clearly not the case. Most people whom quit smoking relapse within one week when withdrawal symptoms peak thereafter relapse occurs but relapse is independent of withdrawal symptoms. With so many eyes on the simplistic nicotine withdrawal syndrome and ready replacement with nicotine products it is no wonder that relapse is so common16.
Cigarettes contain 6 to 11mg of nicotine of which the typical smoker absorbs 1 to 3 mg of nicotine. The typical pack-per-day smoker absorbs 20-40 mg of nicotine achieving plasma concentrations of 25-35 ng per milliliter by the afternoon. In contrast to smoking where rapid absorption of nicotine is possible, the use of nicotine patch and gum provides slower and lower plasma levels of nicotine. Chewing nicotine releases 50% of the nicotine so 10 or 12 doses per day provides 10 mg or so from the 2 mg gum and 20 mg per day from the 4 mg nicotine polacrilex or gum. This is roughly equal to 10 to 15 cigarettes per day. Transdermal nicotine delivers approximately 1 mg of nicotine per hour achieving steady state at a level in 2 or 3 days nearly equal to a pack per day. The new nicotine nasal spray delivers 0.5mg nicotine per pulse and the oral inhaler provides 0.01 mg of nicotine in each 35ml puff. While dependence on the nicotine products is low it is believed that at least 5% of patients continue to use the gum for one year or more. Nicotine is not a treatment for smoking just as alcohol or Bzs are not treatments for alcoholism17.
In one study in a general practice setting the rates of abstinence in the nicotine and placebo groups at two years were 12 and 3 per cent18. Newer treatments are coming from clinical trials to the clinics such as the nicotine inhaler and nasal sprays. Nasal administration systems have been developed to mimic cigarette smoking producing venous plasma concentrations of 5-12 ug/liter. Venous plasma concentrations produced by the spray are lower than those produced by smoking (inhaled nicotine reaches the brain in 7 seconds via arterial boil and venous blood nicotine concentrations peak in 5 minutes) and the rise to peak is also slower than produced by smoking19i. However, these new treatments are short-term and again focused on nicotine and detoxification. Using the non-combustible nicotine inhaler, administered orally, allows weaning from smoking in 17% vs. placebo of 9% at 6 months and 13% vs. placebo at 8% at one year. Subjects averaged six inhalers a day with side effects including throat and mouth irritation and cough19. Experts expect that the nicotine nasal spray and vapor inhaler will be drug delivery systems of abuse, but lower in abuse potential than cigarettes20. Nicotine-based “treatments” may be effective in certain patients for withdrawal but appear best suited as long-term maintenance treatments for patients who can not function without nicotine in the same way that certain opiate addicts can not function without methadone.
Research and much clinical experience over the past several years clearly demonstratesthat the process of addiction involves much more than the addict continuing use to prevent withdrawal. Motivational changes described by the addict as wanting to use, missing the high, preferring the high to “normal state” and the glamorization and psuedodrama of the addict life conspire to make reinitiating of use part of an overall rationalization that this time use will be limited and controlled. Positive reinforcement alone is enough to initiate and maintain addiction. The fact that so many addicts relapse well past detoxification and any influence of withdrawal indicates that the physical dependence model of addiction is alone inadequate. This fact also raises the possibility
that the motivational changes are related to long-term or even permanent shifts in brain function in mesolimbic and frontal areas which are relatively silent but which can bias thinking toward reinitiating use.
The patch, gum, nasal spray, and nicotine inhaler are nicotine replacement therapies that are approximately similar to maintaining heroin addicts on methadone or alcoholics on librium and once stable detoxifying them. The outcomes are also similar. Our work defining the neurobiology of acute withdrawal states brought in to focus the similarities between electrical and chemical stimulation of the noradrenrgic locus coeruleus, spontaneous and precipitated opiate withdrawal, clonidine withdrawal, and nicotine withdrawal. . Giving the missing drug or the alpha-2 adrenergic agonist clonidine could treat all212223. Withdrawal followed by abstinence, both acute and chronic, appears to be difficult to sustain. Part of the problem may be in the hidden withdrawal with anhedonia, dysphoria, and boredom lasting for months. While the autonomic symptoms and signs of opiate, nicotine, alcohol and other drug withdrawal states are more clearly related to a rebound noradrenergic hyperactivity and short-lived, the anhedonia, depression, and boredom may be more attributable to dopamine disruptions and more persistent and related to relapse.
Addictions are chronic disorders not acute conditions. Addiction does not end when the drug is removed from the body (detoxification) or when the acute post drug-taking illnessdissipates (withdrawal). Rather, the underlying addictive disorder persists, and this persistence produces a tendency to relapse to active drug taking. Detoxification does not address the underlying disorder and thus is not adequate treatment. While we have made substantial progress in the acute treatment of withdrawal, the ease or success of withdrawal has little to do with the success of treatment or relapse. Whether the nicotine patch for nicotine dependence, clonidine for opiate dependence, benzodiazepines for alcohol dependence treatments for withdrawal have been successfully developed which decrease the mortality or morbidity associated with “cold turkey” but which are not in themselves treatments. Common to most definitions of dependence are relapse, the compulsion to take the drug with loss of control despite guilt, or thoughts about limiting the use of the drug and a withdrawal or abstinence syndrome of varying intensity. Focusing on the changes induced by drugs which makes relapse more likely than abstinence has led to brain research and new pharmacological treatments.
Since nicotine detoxification is limited in efficacy, Bupropion-HCL –SR (Zyban) has been studied and reported both safe and effective. Bupropion (Zyban) is equal in efficacy to nicotine replacement therapies in acute nicotine withdrawal Bupropion appears unique inits ability to inhibit the noradrenergic locus coeruleus and thereby turn off the brain's withdrawal center24. Bupropion (Zyban) also reduces dropouts and improve abstinence rates of cigarette smokers who are detoxified with the patch and those who stop “cold turkey”. Bupropion (Zyban) increases 4-week continuous abstinence rates among x-smokers. Bupropion (Zyban) efficacy in smoking cessation is reported to be greater than the patch. The combination of the nicotine replacement and the antidepressant are greater in efficacy than the nicotine replacement system alone. While more patients in the company sponsored research succeeded in abstinence using the combination the
effects were not significantly different than Bupropion (Zyban) alone. It is quite compelling to consider that such a treatment reverses acute withdrawal and also have dopaminergic effects that would naturally promote abstinence.
. Bupropion reverses cigarette-withdrawal-related dysphoria and most recently has been clearly demonstrated to reduce cigarette smoking withdrawal relapse. Withdrawal complaints though troubling are not life threatening. Nicotine withdrawal includes irritability; confusion, agitation, insomnia, concentration problems, lethargy, yawning and craving all reversed by smoking. Detoxification and abstinence with social prohibitions is the standard approach to cigarette smoking addiction often referred to as nicotine dependence. The FDA has approved Bupropion-SR (Zyban) for use in reducing smoking cessation-related relapse.
Zyban when given at 300 mg/day for 7 weeks costs approximately $125, Habitrol (21 mg/day for 4 weeks, 14 mg/day for 2 weeks, 7 mg/day for 2 weeks) approximately $215 over-the-counter Nicoderm cq $222 for 8 weeks and Nicotrol 15 mg/day for 6 weeks $129.
Among adults, smoking is decreasing and use is the lowest in nearly three decades. While there is a great deal of popular support for measures that would discourage use of cigarettes, teenage smoking continues to increase. Some of these new smokers learned inhalation of drug vapors by smoking marijuana. Marijuana smoking is a cigarette smoking gateway drug. The national and local public prevention efforts should be coupled with efforts aimed at helping smokers to stop smoking. . The gum and the patch are noteworthy for their low abuse potential and general safety. Transdermal nicotine medications provide about 0.9 mg of nicotine per hour to users averaged over 16-24 hours In contrast the nicotine nasal spray delivers 0.5mg nicotine in a pulse absorbed quickly though the nasal mucosa. Doses can be repeated in quick succession. The nasal inhaler delivers higher doses and delivers nicotine rapidly. The nicotine vapor inhaler requires more training but while providing more of smoking's experience, it delivers less nicotine than the spray. Such treatments may make maintenance treatment feasible for chronic recidivist smokers. New non-nicotine treatments, like Zyban, that are more efficacious than the nicotine replacement treatments and also augment dopaminergic neurotransmission reducing relapse and depression, should make treatment more successful and therefore more accessible from the patients local provider25
1 Henschen,M.,Frischer, T.,Pracht,T., Spiekerkotter,E.,Karmaus,W., Meinert,R.,Lehnert,W., Wehrle,E.,Euehr,J. The internal dose of passive smoking at home depends on the size of the dwelling. Environmental research 72:65-71, 19972 Garfinkel, L., Trends in cigarette smoking in the United States. American Cancer Society, Prevention Medicine 1997 Jul-Aug; 26(4):447
3 MMWR, December 26, 19974 Anda,RF.,Remington,PL.,Sienko,DG.,Davis,RM Are physicians advising smokers to quit:The patients perspective JAMA 1987; 257:1916-1919. 5 Carmody,TP. Preventing relapse in the treatment of nicotine addiction: current issues and future directions. J Psychoactive Drugs 1992; 24:131-158. 6 Glassman,AH.,Helzer,JE.,Covey,LS.,Cottler,LB, Stetner,F.,Tipp,JE., Johnson,J Smoking, smoking cessation and major depression JAMA 264: 1546-1549, 19907 Hall,SM.,Munoz,RF.,Reus,VI Smoking cessation,depression and dysphoria. NIDA RES Monogtr 105:312-313, 19908 Breslau,N.,Kilbey,MM.,Andreski,P Nicotine dependence, major depression and anxiety in young adults. Arch Gen Psychiatry 48:1069-1074,19919 Gilbert,DG. Depression,smoking and nicotine Drug Dev Res 38:267-277, 199610 Fowler,JS.,Volkow,ND.,Wang,GJ.,Pappas,N., Logan,J.,Shea,C., Alexoff,D. MacGregor,RR., Schlyer,DJ.,Zezulkova,I.,Wolf,AP. Brain monoamine oxidase A inhibition in cigarette smokers Proc Natl Acad Sci 93:14065-14069, 199611 Covey, LS. Glassman,AH.,Stetner,F. Major depression following smoking cessation. Am J Psychiatry 154: 263-265, 199712 Gold, MS., Miller, NS.Seeking drugs/alcohol and avoiding withdrawal: The neuroanatomy of drive states and withdrawal. Psychiatric Annals 22:430-435, 199213 O’Brien CP., McLellan, Myths about the treatment of addiction. Lancet 1996;347:237-240. 14 Ockene,JK. Smoking intervention:the expanding role of the physician. Am J Public Health 1987;77:782-783. 15 Law,M.,Tang,JL. An analysis of the effectiveness of interventions intended to help people stop smoking. Arch Intern Med 1995;155:1933-1941. 16 Henningfield,JE. Nicotine medications for smoking cessation. NEJM 1995;333:1196-1203. 17 Johnson,CR.,Gold, MS., Nicotine addiction J Florida M.A. 1996; 83:102-107. 18 Tonnesen,P.,Norregaard,J.,Sawe,U. Two year outcome in a smoking cessation trial with a nicotine patch. J Smok Relat Disord 1992; 3:241-245. 19 Schneider,NG.,Lunell,E.,Olmstead,RE.,Fagerstrom,KO. Clinical pharmacokinetics of nasal nicotine delivery. Clin Pharmacokinet 1996; 1:65-80. 20 Schuh,KJ.,Schuh,LM.,Henningfield,JE.,Stitzer,ML:. Nicotine nasal spray and vapor inhaler:abuse liability assessment. Psychopharmacology 1997;130: 352-361. 21 Miller, NS.,Gold, MS.,Smith,DE. Treatment of detoxification in addictive disorders Miller, NS.,Gold,MS.,Smith,DE. (Eds) Manual of Therapeutics for Addictions Wiley- Liss NY, 1997, pp 97-11022 Glassman,AH., Stetner,F., Walsh,BT.,Raizman,PS.,Fleiss,JL.,Cooper,TB.,Coveyt, LS. Heavy smokers, smoking cessation and clonidine: Results of a double-blind randomized trial JAMA 1988;259:2863-2866. 23 Gold, M.S. and N.S. Miller. “A Hypothesis for a Common Neurochemical Basis for Alcohol and Drug Disorders.” Psychiatric Clinics of North America. 16.1 (March 1993): 105-1724 Nisell, M.,Nomikos,GG.,Svensson,TH., Nicotine dependence, midbrain dopamine systems and psychiatric disorders. Pharmacol Toxicol 1995;76:157-162. 25 Role, LW. Memories and nicotine. Nature 1996; 383:670-671
HIGH ALTITUDE TRAVEL NOTES (Dr Jim Duff, 01/04/2008) More useful information on these and other subjects can be found in my book ‘Pocket First Aid and Wilderness Medicine’, which can be obtained via www.treksafe.com.au . As you ascend to altitudes above 2000m, your body has to acclimatize to the decreasing amount of oxygen available. If the ascent is too fast and/or the height gain
Lezione n.1 DAL LATINO AL VOLGARE (le origini di una lingua) di Pier Paolo Benucci 1° testo INDOVINELLO VERONESE (fine IX secolo) 1° scheda Storia di un indovinello 2° testo ISCRIZIONE DI COMMODILLA (metà IX secolo) 2° scheda Sostrati e lingue neolatine 3° scheda Appendix probi: il volgare nasce dagli errori 3° testo I PLACITI DI MONTECASSINO (960