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Objective: Few studies have examined the potential interactive effect of both smoking and drinking on cognition. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognition. This is the first study to examine the neurocognitive consequences of cigarette smoking combined with chronic alcohol consumption and their relationship to serum BDNF levels in a Chinese Han population., Materials and Methods: We recruited 191 healthy male subjects, including 47 isolated smokers, 31 isolated chronic alcohol users, 58 combined smokers and chronic alcohol users, and 55 non-smokers and non-alcohol users. We then compared the repeatable battery for the assessment of neuropsychological status (RBANS) scores and serum BDNF levels in these four groups., Results: When compared to the non-smoking + non-alcohol-using group, the smoking group performed worse on immediate memory, attention, language, and RBANS total score. There were no significant differences in the RBANS scores between the alcohol-using group and non-smoking + non-alcohol-using group, or between the smoking group and smoking + alcohol-using group. We did not find an association between BDNF and smoking or drinking status or between BDNF and cognitive performance. In the smoking group, there was a significant correlation between BDNF and carbon monoxide concentration, and between BDNF and the Fagerstrom Test for Nicotine Dependence (FTND) total score., Conclusions: Our results suggest that smoking is associated with cognitive decline, but not with BDNF levels in a normal population. However, smoking severity is positively associated with BDNF levels. Concomitant alcohol use does not worsen the cognitive decline caused by smoking.

Purpose: Hemoglobin mass (Hbmass) is commonly assessed using the CO re-breathing method with the subject in the seated position. This may lead to an underestimation of Hbmass as blood in lower extremity veins while seated may not be tagged with carbon monoxide (CO) during the re-breathing period., Methods: To test this hypothesis, CO re-breathing was performed on four occasions in nine male subjects, twice in the seated position and twice in combination with light cycle ergometer exercise (1 W/kg body-weight) intending to accelerate blood circulation and thereby potentially allowing for a better distribution of CO throughout the circulation as compared to in the seated position. Blood samples were drawn from an antecubital vein and the saphenous magna vein following the re-breathing procedure., Results: In the seated position, CO re-breathing increased the percent carboxyhemoglobin (%HbCO) in the antecubital vein to 8.9 % (7.8-10.7) [median (min-max)], but less (P = 0.017) in the saphenous magna vein [7.8 % (5.0-9.9)]. With exercise, no differences in %HbCO were observed between sampling sites. As a result, CO re-breathing in combination with exercise revealed a ~3 % higher (P = 0.008) Hbmass, i.e., 936 g (757-1,018) as compared to 908 g (718-940) at seated rest., Conclusion: This study suggests an uneven distribution of CO in the circulation if the CO re-breathing procedure is performed at rest in the seated position and therefore can underestimate Hbmass.

The purpose of this work was to investigate adaptation and decay from short-term (5-day) heat acclimation (STHA). Ten moderately trained males (mean +/- SD age 28 +/- 7 years; body mass 74.6 +/- 4.4 kg; VO2peak 4.26 +/- 0.37 l min(-1)) underwent heat acclimation (Acc) for 90-min on 5-days consecutively (T (a) = 39.5 degrees C, 60% RH), under controlled hyperthermia (rectal temperature 38.5 degrees C). Participants completed a heat stress test (HST) 1 week before acclimation (Acc), then on the 2nd and 8th day (1 week) following Acc (T (a) = 35 degrees C, 60% RH). Seven participants completed HSTs 2 and 3 weeks after Acc. HST consisted of 90-min cycling at 40% peak power output before an incremental performance test. Rectal temperature at rest (37.1 +/- 0.4 degrees C) was not lowered by Acc (95% CI -0.3 to 0.2 degrees C), after 90-min exercise (38.6 +/- 0.5 degrees C) it reduced 0.3 degrees C (-0.5 to -0.1 degrees C) and remained at this level 1 week later (-0.5 to -0.1 degrees C), but not two (0.1 degrees C -0.4 to 0.5 degrees C; n = 7) or 3 weeks. Similarly, heart rate after 90-min exercise (146 +/- 21 b min(-1)) was reduced (-13: -6 to -20 b min(-1)) and remained at this level after 1 week (-13: -6 to -20 b min(-1)) but not two (-9: 6 to -23 b min(-1); n = 7) or 3 weeks. Performance (746 s) increased 106 s: 59 to 152 s after Acc and remained higher after one (76 s: 31 to 122) but not two (15 s: -88 to 142 s; n = 7) or 3 weeks. Therefore, STHA (5-day) induced adaptations permitting increased heat loss and this persisted 1 week but not 2 weeks following Acc.

Rationale: A dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated., Objectives: The present study evaluated the relationship between carrying the DRD4 VNTR 7-repeat allele and transient functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent responses to smoking cues among adult dependent cigarette smokers., Materials and Methods: Smokers (n = 15) underwent fMRI scanning after 2-h abstinence. During scanning, they viewed visual smoking and control cues. A blood sample was assayed for the DRD4 VNTR polymorphism, and participants were categorized based on whether they carried one or two copies of the 7-repeat allele (DRD4 L, n = 7) or not (DRD4 S, n = 8)., Results: Contrasts in brain cue-reactivity (smoking minus control cues) between DRD4 groups were conducted using SPM2. Smoking cues as compared to control cues elicited transient brain responses in right superior frontal gyrus (BA 8/9/10/32), left anterior cingulate gyrus (BA 32), and right cuneus (BA 19). Exposure to smoking cues resulted in greater activation of right superior frontal gyrus (BA 10) and right insula in DRD4 L compared to DRD4 S individuals. By contrast, exposure to smoking cues among DRD4 S individuals resulted in no significant increases in activation compared to DRD4 L individuals., Conclusions: These brain imaging results suggest that DRD4 VNTR polymorphism is related to transient brain responses to smoking cues in regions subserving executive and somatosensory processes.

Total haemoglobin mass can be easily measured by applying the optimised CO-rebreathing method (oCOR-method). Prerequisite for its accurate determination is a homogenous CO distribution in the blood and the exact knowledge of the CO volume circulating in the vascular space. The aim of the study was to evaluate the mixing time of CO in the blood after inhaling a CO-bolus and to quantify the CO volume leaving the vascular bed due to diffusion to myoglobin and due to exhalation during processing the oCOR-method. The oCOR-method was also compared to a former commonly used CO-rebreathing procedure. In ten subjects, the time course of carboxy-haemoglobin (HbCO) formation was analysed simultaneously in capillary and venous blood for a period of 15 min after inhaling a CO bolus. The volume of CO diffusing from haemoglobin to myoglobin was calculated via the decrease of HbCO. As part of this decrease is due to CO exhalation, this volume was quantified by collecting the exhaled air in a Douglas bag system. Equal HbCO values in capillary and venous blood were reached at min 6 indicating complete mixing of CO. The loss of CO out of the vascular bed due to exhalation and due to diffusion to myoglobin was 0.32 +/- 0.12% min(-1) (0.25 +/- 0.09 ml min(-1)) and 0.32 +/- 0.18% min(-1) (0.24 +/- 0.13 ml min(-1)) of the administered CO volume, respectively. The loss of CO due to exhalation and diffusion to myoglobin is of minor impact. It should, however, be considered by using correction factors to obtain high accuracy when determining total haemoglobin mass.

Rationale: Compensation or compensatory smoking, accurately defined, deals with the question of whether switching to cigarette brands with different smoke yields is associated with a change in smoke uptake proportional to the change in machine-derived yields. The issue of compensation is important because it bears on whether switching to "lighter" brands means lower overall smoke intake or not., Objectives: The present review investigated whether and to what extend low yield cigarettes are smoked more intensively. In addition, published data on whether nicotine, "tar", or any other smoke constituent or property influence compensational smoking are summarized., Methods: The studies on compensation were classified as follows: (1) studies on smoking behaviour in relation to cigarette yields (with and without brand switching); (2) studies on compensation for nicotine (switching between cigarettes which differ "only" in their nicotine yield, nicotine supplementation, manipulation of renal nicotine excretion, administration of nicotine agonists or antagonists); (3) studies on compensation for other factors (influence of tar, taste, irritation, draw resistance). In order to quantify the degree of compensation, an index is defined and applied to selected brand switching studies. This compensation index determines, in relative units, the degree to which a smoker responds to a change in smoke yields with a change in smoke uptake measured by suitable biomarkers. The role of vent blocking is also briefly discussed., Results: Most of the studies which compare the smoking behaviour when smoking cigarettes with different smoke yields supply evidence for "partial" compensation, suggesting that cigarettes with lower yields are smoked more intensively than those with higher yields. These studies also show that a change in the daily number of cigarettes is not a common mechanism of compensation. Effective vent blocking during smoking is a rare event and can therefore also be regarded as an uncommon mechanism of compensation. Evaluation of a suitable subset of brand-switching studies revealed an average compensation of 50-60% of the nicotine yield. Compensation tended to be more complete when changing to cigarettes with higher yields than when changing to cigarettes with lower yields. In general, brand-switching studies do not supply information on the underlying causal factors responsible for compensatory smoking. Results of the nicotine supplementation studies are not conclusive: some report evidence of nicotine titration, others do not. A general problem with this type of investigation is that continuous nicotine application does not mimic the spike-wise application with cigarette smoking, and may lead to nicotine tolerance. There is limited evidence that cigarettes were smoked more intensively when the urinary clearance of nicotine was increased. A small number of studies provide some evidence that smoking intensity increased after smokers were administered a nicotine antagonist. Several reports indicate that tar, taste and sensory properties of the smoke as well as the draw resistance of the cigarette may play a role in compensatory smoking. Low-yield cigarettes usually have reduced pressure drops which smoke researchers have suggested leads to increased puff volume. This effect seems to be independent of the smoke yield of the cigarette. There is also some evidence that some smokers maintain a consistent pattern of smoking which works independent of any changes in nicotine or tar yields, taste or design features of the cigarette ("functional autonomy")., Conclusions: The available data suggest that smokers partially compensate for a different smoke yield. While the factors and their interaction responsible for compensational smoking are not fully understood, there are data suggesting that a subgroup of smokers may partially compensate for nicotine. Even in this subgroup of smokers, however, the relative importance of the pharmacological versus

Nicotine nasal spray (NNS) is generally considered to be an effective smoking cessation aid, but all studies to date of NNS effectiveness have also utilized group therapy sessions or frequent laboratory visits to support their subjects' stop smoking efforts. We studied 50 volunteers before they attempted to quit smoking and again at 1, 2 and 3 months after they received NNS to assist them in quitting smoking. No other stop smoking intervention was used, which more closely mimics the common practice of many individuals trying to stop smoking with the aid of a nicotine replacement product but without other supportive interventions. We found that 50% of the subjects quit smoking for the first month, 34% were still abstinent after 2 months and 32% quit smoking for 3 months. Those who quit smoking for the entire 3 months and who continued regular NNS use throughout had 67% cotinine replacement at the end of the first month, while another group which quit smoking for only the first month with the aid of NNS had 42% cotinine replacement at the end of that month. Our data confirm that NNS is an effective smoking cessation aid, but our abstinent rate at 3 months is slightly lower than in other studies in which group therapy was provided. Our data also indicate that higher NNS-induced cotinine replacement during the first month of quitting smoking (suggesting more frequent use of NNS) is associated with longer term quit-smoking success rate.

Acoustic prepulse inhibition (PPI) refers to the reduction of the startle reflex to an intense stimulus if it is preceded by a weak stimulus. Nicotine and smoking have been reported to enhance PPI in rats and in healthy men, respectively. We studied the influence of smoking on PPI in healthy men and women, comparing non-smokers, deprived smokers, and smokers smoking during the test session after deprivation or after ad libitum smoking. Smoking during the session enhanced PPI, without affecting startle reaction or habituation over time. In addition, the effect of smoking on PPI was gender dependent. In men, ad libitum smoking enhanced PPI compared with non-smokers, while, in women, deprivation reduced PPI and smoking restored PPI to the level of non-smokers.

Unlabelled: We report two cases of unexpected courses of inhalation anaesthesia with sevoflurane and enflurane which were caused by the presence dry soda lime. Case 1: During mask induction of a healthy 46-year-old female patient for elective hysterectomy it was noted that the vaporizer setting of 5% sevoflurane (in 50% O2, 50% N2O) did not result in the expected increase of inspiratory sevoflurane concentration. At the same time, the anaesthesiologist observed that the patient did not lose consciousness while the temperature of the soda lime canister increased sharply and the colour of the soda lime turned to blue with condensing water visible in the tubing. It was later determined that this anaesthesia machine had not been used for more than 2 weeks. Analysis of the soda lime showed a water content of <1%. Case 2: Following intravenous induction of a non-smoking 64-year-old male patient for elective gastrectomy, it was noted that the concomitant inhalation of enflurane was associated with a sharp rise in the temperature of the soda lime canister, a colour change of the soda lime to blue and a decrease in the measured inspiratory enflurane concentration despite an unchanged or even increased vaporizer setting. Arterial blood gas analysis revealed a CO-Hb concentration of 8.8% with otherwise normal acidity and partial gas pressures. Immediate change of the absorbant resulted in a decline in the CO-Hb concentration to 6.9% within 3 h. It was later determined that the anaesthesia machine had not been used for 34 h. Analysis of the soda lime showed a water content of 5.4%., Discussion: Both case reports were associated with a rise in temperature and a colour change to blue of the soda lime. Reactions of desflurane, enflurane or isoflurane with dry soda lime resulting in significant CO-Hb formation have been previously reported. Reactions of sevoflurane with dry soda lime have been observed but have so far not been published. Until further analysis of these phenomena is completed, it is mandatory for the patient's safety to guarantee that only soda lime with a sufficient water content be used for clinical anaesthesia.

Objectives: Due to its low solubility and negligible metabolism, desflurane is assumed to be especially suitable for application by low-flow anaesthetic techniques. The aim of this clinical investigation was the development of a standardised dosing scheme for low-flow and minimal-flow desflurane anaesthesia., Methods: One hundred six ASA status I-II patient were assigned to six groups according to the duration of the initial high-flow phase, fresh gas flow, and fresh-gas desflurane concentration. The median age, height, body weight, and constitution of the groups was comparable. After an initial high-flow phase using 4.4 l/min, the fresh gas flow was reduced to 0.5 l/min (minimal-flow anaesthesia) or 1.0 1/min (low-flow anaesthesia). Inspired nitrous oxide concentrations were maintained at 60% to 70%. Using different standardised schemes of vaporizer settings, inspired desflurane concentrations were applied in the range from 3.4% to 8.7%, i.e., between 1 and 1.5 MAC. Inspired and expired desflurane concentrations were measured continuously by the side-stream technique and recorded on-line. Venous blood samples were taken immediately prior to induction and 45 min after flow reduction for measurement of carboxyhaemoglobin (COHb) concentration)., Results: In the 10- to 15-min initial phase during which a high fresh gas flow of 4.4 l/min was used, the inspired desflurane concentration reached values in the range of 90%-95% of the fresh gas concentration. In low-flow anaesthesia this concentration could be maintained without any alteration of the vaporizer setting, whereas in minimal-flow anaesthesia with flow reduction the fresh gas concentration had to be increased by 1% to 2%: The quotient calculated by division of the inspired desflurane concentration by its fresh gas concentration (Q = CI/CF) ranges between 0.65 and 0.75 in animal-flow and between 0.80 and 0.85 in low-flow anaesthesia. If use was made of the wide output range of the desflurane vaporizer, the inspired concentration could be increased rapidly by about 5% in 8 min, although the flow was kept constant at 0.5 l/min. Compared with its value prior to induction (2.13 +/- 1.05%), the COHb concentration decreased statistically significantly by about 0.7% during the 1st hour of minimal-flow anaesthesia (1.42 +/- 1.01%). In no case was a COHb concentration observed that exceeded threatening or even toxic values, although the soda lime was changed routinely only once a week., Conclusions: The pharmacokinetic properties of desflurane, resulting in especially low individual uptake, and the wide output range of the vaporizer facilitate the use of low-flow anesthetic techniques in routine clinical practice. Even in minimal-flow anesthesia, the duration of the initial high-flow phase can be shortened to min. If the flow is reduced to 1 l/min, the inspired desflurane concentration achieved in the initial high-flow phase can be maintained without any alteration of the vaporizer setting. In minimal-flow anesthesia, however, with flow reduction to 0.5 l/min, the fresh gas concentration has to be increased to a value 1%-2% higher than the inspired nominal value. Due to the wide dialing range of the desflurane vaporizer, the amount of vapour delivered into the breathing system can be increased to about 110 ml/min even at a flow of 0.5 l/min. The large amount of agent that can be delivered into the system even under low-flow conditions, together with the very low individual uptake, results in a time-constant that is sufficient short for the clinically required rapid increase in inspired desflurane concentrations. The short time-constant of low-flow desflurane anaesthesia improves the control of the anaesthetic concentration. If all measures are taken to safely avoid inadvertent drying out of the soda lime, there is no evidence that low-flow anaesthesia with desflurane is liable to increase the risk of accidental carbon monoxide poisoning. (ABSTRACT TRUNCATED)

In this study, we report on the comparability of the subjective experience and smoking style elicited by two commercially available cigarettes which differ in nicotine levels, one containing a 'regular' delivery of 0.7 mg and the other containing minimal (0.1 mg) nicotine. Our findings suggest subtle differences in the smoking of these two cigarettes, with the 'denicotinised' cigarette being smoked for longer and with more puffs taken. While these subtle differences have little significance for studies concerned with the effects of nicotine on cognitive performance measures, they are certainly important for studies concerned with the role of nicotine in maintaining smoking behaviour.

The duration of behavioral impairment after marijuana smoking remains a matter of some debate. Alcohol and marijuana are frequently used together, but there has been little study of the effects of this drug combination on mood and behavior the day after use. The present study was designed to address these issues. Fourteen male and female subjects were each studied under four conditions: alcohol alone, marijuana alone, alcohol and marijuana in combination, and no active treatment. Mood and performance assessments were made during acute intoxication and twice the following day (morning and mid-afternoon). Acutely, each drug alone produced moderate levels of subjective intoxication and some degree of behavioral impairment. The drug combination produced the greatest level of impairment on most tasks and "strong" overall subjective ratings. There were few significant interactions between the two drugs, indicating that their effects tended to be additive. Only weak evidence was obtained for subjective or behavioral effects the day after active drug treatments, although consistent time-of-day effects (morning versus afternoon) were observed on several subjective and behavioral measures. In sum, this study provided little evidence that moderate doses of alcohol and marijuana, consumed either alone or in combination, produce behavioral or subjective impairment the following day.

There were two experiments on abstinence from smokeless tobacco. The purpose of the first experiment was to determine abstinence effects from smokeless tobacco. The purpose of the second experiment was to examine the effects of different doses of nicotine gum on smokeless tobacco abstinence effects. The subjects were male Copenhagen smokeless tobacco users who underwent 3 days of baseline measurement while continuing to use smokeless tobacco ad libitum, and 5 days of the experimental condition. In the first experiment, the subjects were assigned randomly to one of two groups and compared: continuous smokeless tobacco users (n = 10), and deprivation plus no nicotine gum (n = 10). In the second experiment, subjects were assigned randomly and in a double-blind fashion to one of three groups and compared: (1) deprivation plus 0 mg nicotine gum (n = 20); (2) deprivation plus 2 mg nicotine gum (n = 20); and (3) deprivation plus 4 mg nicotine gum (n = 20). The first experiment showed significant increases upon abstinence for the following variables: (1) craving; (2) difficulty concentrating; (3) restlessness; (4) excessive hunger; (5) eating; (6) reaction time; (7) variability of reaction time and (8) total withdrawal scores for both the self-rated and the observer-rated forms. The second experiment showed that nicotine gum failed to significantly reduce smokeless tobacco abstinence effects, although those with high cotinine levels may receive some benefit from nicotine gum.

Five male smokers were tested, after 48-h abstention from tobacco-product use, smoking a leading "lights" category cigarette (Control-FTC nicotine yield 0.6 mg) and another cigarette yielding similar amounts of "tar" and carbon monoxide (CO), but only 0.06 mg nicotine (Test). Heart rate (HR) and the electroencephalogram (EEG) were monitored before, during and after the smoking of each cigarette. Other measures obtained included the subjects' puffing and breathing behaviors during smoking, plasma nicotine concentrations, blood carboxyhemoglobin concentrations and expired-air CO. The results indicated no significant differences in the way the subjects puffed and inhaled the two cigarettes and they were therefore assumed to have inhaled similar amounts of particulate matter and gas-phase components. Plasma nicotine concentrations were significantly higher following smoking of the Control cigarette. HR (percent relative change) increased following smoking of either cigarette; however, HR increase was significantly greater following smoking of the Control cigarette. Smoking the Test cigarette had no effect on the EEG. Smoking the Control cigarette produced a significant increase in beta 2 magnitude and a significant decrease in delta magnitude. This indicates that the effects of smoking on the EEG are a function of nicotine absorbed from cigarette smoke upon inhalation and not a function of inhaled particulate matter, CO, or other gas-phase components.

Two experiments assessed subjective and hormonal effects of smoking cigarettes with three different nicotine deliveries. In experiment 1, 12 males smoked two cigarettes on three different occasions: (1) nicotine-free; (2) their own brand (1.0 mg FTC-estimated nicotine delivery); or (3) 2.4 mg FTC nicotine cigarettes. In experiment 2, 12 males smoked cigarettes of comparable nicotine yield using a quantified smoke delivery system (QSDS). Blood was sampled 2 min after each cigarette completion. Relative to nicotine-free smoking, plasma beta-endorphin (BE) and serum cortisol concentrations increased after quasi-ad libitum smoking of 2.4 mg, but not after 1.0 mg nicotine cigarettes. Self-reported malaise (nausea, sickness, and unpleasantness) also increased after smoking 2.4 mg nicotine cigarettes; subjective distress was correlated with changes in blood BE and cortisol. Smoking 1.0 mg cigarettes did not increase BE or cortisol, or subjective distress. QSDS smoking produced hormonal and subjective effects similar to quasi-ad libitum smoking; however, correlations between neuromodulator concentrations and mood were non-significant. These findings suggest that the elevated levels of plasma BE and cortisol reported in some smoking studies may not be characteristic effects of normal smoking.

The present study examined the effects of systematic manipulation of breathhold duration (0 and 20 s) on the physiological and subjective response to active (M; 2.3% delta-9-THC) and placebo (P; 0.0% delta-9-THC) marijuana in a group of ten regular marijuana smokers. During the eight-session experiment, subjects were exposed twice to each of four experimental conditions (P0, P20, M0, M20), scheduled according to a randomized block design. A controlled smoking procedure was used in which the number of puffs and puff volume were held constant. Expired-air carbon monoxide (CO) levels were used to monitor smoke intake. Breathhold duration affected CO absorption; significantly more CO was absorbed from both P and M smoke after 20 s of breathholding (mean CO boost = 6.9 ppm) than after no breathholding (mean = 4.4 ppm). Heart rate was minimally affected by the breathhold manipulation. Effects of marijuana on mood were not consistently affected by breathhold duration. The results confirm previous findings that prolonged breathholding does not substantially enhance the effects of inhaled marijuana smoke.

The present study compared for the first morning cigarettes CO and nicotine absorption as well as the effects on EEG and peripheral functions across a period of 90 min. Eighteen smokers participated in two sessions, one in which they smoked two cigarettes in succession and another in which they smoked three cigarettes at 30-min intervals. Smoking two cigarettes in succession produced a particularly wide range in nicotine absorption so that the subjects could be grouped into high (HN) and low (LN) nicotine absorbers, differing significantly in their CO and nicotine absorption. The smoking-induced cardioacceleration was greater and lasted longer in the HN than in the LN group. While the dominant alpha frequency increased to a significant extent in the HN group only, beta power increased in both groups, alpha power remained unaffected, theta power decreased in the HN group only and the effects on heart rate, dominant alpha frequency and beta power were significantly correlated with nicotine absorption across both groups. Smoking three cigarettes at 30-min intervals produced qualitatively similar but generally smaller effects. However, neither nicotine uptake nor any of the physiological parameters showed differential developments between the two groups, except the dominant alpha frequency, which increased in the HN group only. The development of acute tolerance to smoking across three cigarettes was observed only for finger vasoconstriction, craving to smoke and sickness after smoking, but not for cardioacceleration or any EEG parameters.

A rapid and reliable method of carboxyhemoglobin determination is described. Hemoglobin-bound carbon monoxide is released chemically into a continuous nitrogen stream and transported to an infrared gas analyser. The total amount of released CO is determined electronically. 100% CO Hb values are obtained in the same way from diluted blood samples after flushing with pure CO in special saturation vessels. The method described yields results with a standard deviation of +/- 2.5%.

The discriminative stimulus (DS) effects of smoked marijuana were studied by training marijuana smokers to discriminate between the effects of marijuana containing 2.7% delta 9-THC (M) and marijuana containing 0.0% delta 9-THC (P). In addition to measures of discrimination responding, subjective effects were assessed with standardized mood questionnaires. The post-smoking increase in expired air carbon monoxide (CO) level was used as an index of smoke inhalation. Relative to P cigarettes, M cigarettes increased heart rate and produced changes on eight mood scales. M cigarettes were rated as harsher and more potent than P cigarettes, and produced lower levels of CO than P cigarettes. The P--M discrimination was readily acquired by most subjects. The DS effects of marijuana showed a rapid onset, appearing within 90 s from the beginning of smoking. The DS effects were dose dependent, with 0.9% delta 9-THC marijuana producing primarily placebo-appropriate discrimination responding, and 1.4% delta 9-THC marijuana producing 100% drug-appropriate responding. This experimental paradigm could be used to determine whether the DS effects of smoked marijuana would generalize to those of other psychoactive drugs.

The carboxyhemoglobin (COHb) level was estimated in patients attending an anti-smoking clinic. A surprisingly large fraction of patients that reported "no smoking" were found to have abnormally high COHb. We believe that this discrepancy is due to the patients not reporting their smoking habits correctly. This phenomenon is further evidence that smoking should be regarded as a form of drug addiction in some persons. Some early relapses in stop-smoking programs can apparently be explained by the patient's admitting previously concealed smoking. For scientific purposes the results of stop-smoking cures should be evaluated by other means than the patient's own reports.

Tissue carbon monoxide (CO) content was investigated in rats severely intoxicated with CO under various exposure conditions: 1% CO for 4 min, 0.4% CO for 40 min and 0.12% CO for 12 h. Extravascular CO was determined in the heart and skeletal muscles immediately after termination of exposure, and carboxymyoglobin (MbCO) percent saturation was calculated. Total brain CO was estimated immediately after termination of exposure and after the time periods of restitution. After the same exposure conditions, MbCO percent saturation was higher in the heart than in skeletal muscle. In both types of muscle, saturation of myoglobin (Mb) with CO depended on blood carboxyhemoglobin (HbCO) level and not on the duration of exposure. The time course of CO elimination was the same for blood and brain, irrespective of CO exposure conditions. The results obtained showed that acute CO intoxication induced by long duration exposures did not involve CO accumulation in the tissues.

Carrier-free 11C-labeled carbon monoxide was produced by proton irradiation of a nitrogen gas flow target via the 14N(p, alpha)11C process followed by on-line reduction of the predominantly formed 11C-carbon dioxide with a yield of 0.4 mCi/muAmin. After appropriate quality control about 2 mCi of carrier-free 11C-carbon monoxide in 500 ml on nitrogen gas were inhaled by test subjects in one breath. The 11C-activity distribution was then followed in vivo by scanning above thorax, head, liver, thigh and os sacrum; simultaneously the 11c-activity of the blood was also followed by batch measurement. The data indicate that part of the 11C-activity migrates from the blood into the intercellular space, while another part is exhaled. The 11C-activity leaves the individual organs with a biological half-life ranging from about 120 to 200 min, a time which is short as compared to the one observed for 51Cr-labeled erythrocytes. A radio gas chromatographic analysis of the exhaled air showed that the 11C-activity leaves the body exculsively in the form of 11C-labeled carbon monoxide. Consequently, metabolism of the 11CO into 11CO2 or other compounds can be excluded.

A specific objective of this 6-week crossover study was to determine how 21 regular smokers of middle tar cigarettes changed their smoking behaviour and uptake of smoke constituents, when switching to either lower tar cigarettes capable of delivering amounts of nicotine similar to a conventional middle tar cigarette (maintained nicotine product), or to conventional low tar/low nicotine cigarettes. Subjects visited the laboratory every 2 weeks for detailed assessment of their smoking behaviour. Weekly per capita consumption was similar for all three cigarettes. They were smoked with variable intensities (low tar greater than maintained nicotine greater than middle tar), the tendency being for larger puff volumes, faster puffing and increased puff duration with the low tar cigarettes. The maintained nicotine cigarette was preferred to the middle tar cigarette, although acceptability ratings of the three cigarettes only differed marginally. The nicotine absorbed from the maintained nicotine and middle tar cigarettes was similar and significantly greater than the levels achieved from the low tar cigarettes. Intake of carbon monoxide into the mouth and absorption into the blood stream was lower for the maintained nicotine cigarette than for the middle tar cigarette, with the low tar cigarette occupying an intermediate position. Derived estimates of tar intake suggested reduced intake of tar into the respiratory tract (around 25%) from the maintained nicotine product relative to the middle tar product. The possible advantages of switching to maintained nicotine cigarettes is discussed.