Search

Rationale: Nicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have examined the effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior., Objective: The primary aim of this within-subject, double-blind study was to examine whether transdermal nicotine replacement (0 mg vs 21 mg/day) altered response to a low-dose priming drink and subsequent ad libitum drinking behavior., Materials and Methods: Subjects (n=19) were non-treatment-seeking, non-dependent heavy drinkers who were daily smokers. Six hours after transdermal patch application, subjective and physiological responses to a priming drink [designed to raise blood alcohol levels (BALs) to 0.03 g/dl] were assessed. This was followed by a 2-h self-administration period where subjects could choose to consume up to eight additional drinks (each designed to raise BALs by 0.015 g/dl) or to receive monetary reinforcement for drinks not consumed., Results: We found that 6 h after patch application, tobacco craving associated with withdrawal relief was decreased, and systolic blood pressure and heart rate were increased in the active patch condition compared to the placebo patch condition. Subjective intoxication in response to the priming drink was attenuated in the active nicotine patch condition compared to 6 h of nicotine deprivation (i.e., placebo patch). During the self-administration period, subjects had longer latencies to start drinking and consequently appeared to consume fewer drinks when administered the active patch compared to the placebo patch., Conclusions: In heavy drinkers, transdermal nicotine replacement compared to mild nicotine deprivation attenuated subjective and physiological alcohol responses and delayed the initiation of drinking.

Rationale: Although 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones., Objectives: In this study, the physiological and subjective effects of MDMA in humans were determined at cold (18 degrees C) and warm (30 degrees C) ambient temperatures in a temperature and humidity-controlled laboratory., Methods: Ten healthy volunteers who were recreational users of MDMA were recruited. Four laboratory sessions were conducted in a 2x2 design [i.e., two sessions at 30 degrees C and two at 18 degrees C, two during MDMA (2 mg/kg, p.o.) and two during placebo, in double-blind fashion]. Core body temperature (ingested radiotelemetry pill), skin temperature (four weighted sites), heart rate, blood pressure, metabolic rate (indirect calorimetry), shivering (electromyogram levels), and sweat rate (capacitance hygrometry) were measured as well as subjective effects for several time periods following capsule ingestion., Results: MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions. MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported. There were no differences related to ambient temperature for any of the subjective effects, except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA., Conclusions: Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.

Rationale: Clozapine inhibits sympathetic outflow to the cutaneous vascular bed. Clozapine reverses hyperthermia and cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) or by lipopolysaccharide (LPS). Clozapine also reverses cutaneous vasoconstriction elicited by exposure to cold. These actions distinguish clozapine from haloperidol. Clozapine could also inhibit sympathetic cutaneous vasomotor alerting responses (SCVARs), vasoconstrictor episodes that reflect emotional/psychological function, and this property might also distinguish clozapine from haloperidol., Objectives: Experiments in rats determined whether clozapine and haloperidol inhibit SCVARs, and whether SR46349B (a 5HT2A receptor antagonist), 8-OH-DPAT (a 5-HT1A agonist), L741,626 (a dopamine D2 antagonist) or SCH23390 (a dopamine D1 antagonist) have clozapine-like effects on SCVARs., Methods: Mean level and pulse amplitude of the tail artery Doppler flow signal were recorded in conscious freely moving rats before and after alerting stimuli (e.g. tapping the cage), and expressed as a SCVAR index (fall to zero flow implies SCVAR index of 100%, no fall implies 0%)., Results: Clozapine (0.0625-1.0 mg/kg, s.c.) dose-dependently increased resting tail blood flow. After 1 mg/kg, the SCVAR index was 18+/-1%, compared with 83+/-2% after vehicle. SR46349B (0.01-1.0 mg/kg) and 8-OH-DPAT (0.25 mg/kg) had similar but less potent effects on cutaneous blood flow and on SCVARs. Haloperidol (0.005-0.5 mg/kg) and L741,626 (1 mg/kg) had no or little effect on these variables. SCH23390 mildly inhibited SCVARs., Conclusions: Clozapine, but not haloperidol, increases resting cutaneous blood flow and decreases SCVARs. Antagonism at 5-HT2A receptors and agonism at 5-HT1A receptors could contribute to these actions.

Rationale: Parametric preclinical studies of the benzodiazepine antagonist flumazenil have contributed to the understanding of the physical dependence associated with chronic benzodiazepine use. However, few parametric studies have been conducted in human participants., Objective: This study was designed to assess the effect of duration of benzodiazepine exposure on the intensity of flumazenil-precipitated withdrawal in healthy volunteers., Method: Participants were randomly assigned to receive either oral diazepam (15 mg/70 kg; n=10) or placebo (n=8) capsules nightly for 28 days. Effects of flumazenil (1 mg/70 kg, intravenously administered) were assessed in challenge sessions conducted before capsule ingestion, and after 1, 7, 14, and 28 days of capsule ingestion., Results: Flumazenil produced a profile of participant-rated effects consistent with benzodiazepine withdrawal that peaked immediately after completion of the 5-min flumazenil injection and rapidly dissipated thereafter. The magnitude of these effects was comparable after 7, 14, and 28 days of diazepam. Flumazenil also produced modest elevations in blood pressure and decreases in skin temperature in the diazepam group, both of which were sustained throughout the approximate 60-min session., Conclusions: These findings support previous human research studies indicating that flumazenil precipitates withdrawal after short chronic exposure to benzodiazepines and suggests that duration of exposure does not influence the intensity of withdrawal beyond the first week of exposure.

Rationale: The majority of pharmacotherapies proposed for cocaine dependence have been marginally effective and frequently have undesirable side effects. We recently demonstrated that short-term treatment with citicoline decreased self-reported desire to use cocaine in crack cocaine users., Objective: The present study was conducted to assess the safety of citicoline in combination with cocaine by investigating whether cocaine-induced cardiovascular and behavioral effects and cocaine plasma levels are altered by citicoline pretreatment., Methods: Eight healthy male and female volunteers who used cocaine on an occasional basis participated in this randomized, placebo-controlled, three-visit study. During all three visits, subjects received an acute intranasal dose of cocaine (0.9 mg/kg) and were continuously monitored for the ensuing 3.5 h. The first visit involved no pretreatment, and visits 2 and 3 were preceded by a 4-day pretreatment period of either citicoline (1 g/day) or placebo., Results: Citicoline pretreatment did not alter the cardiovascular, physiologic, or subjective effects of acute cocaine., Conclusions: Although citicoline did not block the acute subjective effects of cocaine in a laboratory environment, the combined use of citicoline and a moderate dose of intranasal cocaine presented no added risk of cardiovascular effects. Further study is necessary to determine whether this medication (which is currently used to treat strokes) will be a useful adjunct to treat cocaine dependence.

Rationale: Although the behavioral, subjective, and physiological effects of oral cocaine have been investigated, its reinforcing effects have not been demonstrated., Objective: The primary aims of this study were to examine the reinforcing effects of oral cocaine and determine whether such effects can be influenced by manipulating behavioral requirements following drug ingestion., Methods: Nine adult volunteers with histories of cocaine abuse were trained to discriminate between orally administered cocaine (100 mg/70 kg) and placebo capsules under double-blind conditions. Following acquisition of cocaine vs placebo discrimination (80% correct), the reinforcing effects of cocaine were determined using two different choice conditions (dependent and independent). Volunteers were first exposed to cocaine and placebo once each with a relaxation activity (sitting in a cushioned chair) and a vigilance activity (performing a computer task). Following exposure to each drug with each activity, volunteers began the dependent choice condition. Every 2 days volunteers chose which drug (cocaine or placebo) they ingested with the vigilance and relaxation activities. Volunteers could not choose the same drug with both activities. This procedure occurred 5 times over a 10-day period. The independent choice condition took place over 2 days. On one day, volunteers chose which drug (cocaine or placebo) they ingested with the relaxation activity and, on the other day (in counterbalanced order), which drug they ingested with the vigilance activity. Volunteers were allowed to select the same drug with both activities., Results: All volunteers successfully acquired the cocaine vs placebo discrimination. In the dependent choice condition, all volunteers significantly chose cocaine over placebo with the vigilance activity and chose placebo over cocaine with the relaxation activity. In the independent choice condition, volunteers significantly chose cocaine over placebo with the vigilance activity (i.e., cocaine functioned as a positive reinforcer in the vigilance context). Interestingly, the independent choice condition also showed that volunteers chose placebo over cocaine with the relaxation activity (i.e., cocaine functioned as a negative reinforcer because it was avoided relative to placebo)., Conclusion: The study shows that the behavioral requirements following drug ingestion can be a determinant of whether or not oral cocaine functions as a reinforcer in volunteers with histories of cocaine abuse.

Rationale: Psychomotor stimulants previously have been found to increase the frequency of cigarette smoking, but it is unclear whether this is due to a non-specific increase in general activity or a specific increase in the reinforcing effects of smoking., Objectives: To investigate whether d-amphetamine increases the relative reinforcing effects of cigarette smoking., Methods: Ninety minutes after d-amphetamine (7.5, 15 mg/70 kg) or placebo administration, 13 male and female subjects participated in 3-h sessions during which they could make a maximum of 20 choices between cigarette smoking (two puffs per choice), earning money ($0.25 per choice), or neither. In separate sessions, using the same subjects, the effects of d-amphetamine on the frequency of ad libitum smoking was assessed., Results: During choice sessions, d-amphetamine dose-dependently increased smoking choices from 4.2 +/- 0.6 to 5.7 +/- 0.6. During sessions in which subjects smoked ad libitum, d-amphetamine increased number of cigarettes smoked from 2.8 +/- 0.4 to 3.8 +/- 0.6. Breath carbon monoxide (CO) levels, a measure of smoke exposure, showed corresponding dose-related increases., Conclusions: These results are consistent with previous findings that d-amphetamine increases smoking and provide evidence that this effect is due to a drug-produced increase in the relative reinforcing effects of cigarette smoking.

Rationale: Clinical data suggest that stimuli paired with cocaine use acquire emergent stimulus effects, such as the ability to elicit cocaine craving., Objectives: The purpose of this study was to determine the conditioned effects of neutral stimuli paired with cocaine smoking., Methods: Eight experienced adult cocaine smokers participated in 22 experimental sessions while residing on a Clinical Research Center. One set of cues (CS-) was paired with placebo smoked cocaine and one set of cues (CS+) was paired with 25 mg smoked cocaine., Results: After 18 training trials, the effects of cocaine on heart rate and ratings of "anxious" were greater, and skin temperature and ratings of "tired" were smaller when compared to the effects of cocaine after the first training trial. When instructed to select a cue to experience after training, seven of eight participants selected the CS+, while only three of the participants selected the CS+ prior to training, i.e., the CS+ functioned as a conditioned reinforcer. Presentation of the CS+ alone without cocaine during extinction trials increased HR, SP, and ratings of "anxious" "tired", and "I want cocaine" and decreased skin temperature. These changes elicited by presentation of the CS+ decreased over the course of the extinction sessions., Conclusions: The present results indicate that classical conditioning is one mechanism by which stimuli paired with cocaine acquire emergent stimulus effects.

Psychopharmacological studies using caffeinated beverages or caffeine have rarely considered temporal effects on psychological and physiological function or the specific contribution of caffeine, hot water, or beverage type to the observed effects. The effect of 400 ml hot tea, coffee, and water consumption on systolic and diastolic blood pressure (SBP and DBP), heart rate, skin conductance (a measure of sympathetic nervous system activation), skin temperature, salivary cortisol, and mood were monitored in 16 healthy caffeine-withdrawn (14 h) subjects in a complete crossover design. Beverages were ingested with/without 100 mg caffeine and milk (tea/coffee only). Hot beverage ingestion rapidly increased skin conductance and temperature (+1.7 degrees C) with peak effects observed only 10-30 min post-consumption. Caffeine in the beverage rapidly augmented skin conductance responses but, in contrast to the effect of hot water, reduced the skin temperature response and increased SBP (+2.8 mmHg) and DBP (+2.1 mmHg) 30-60 min post-consumption. Both caffeine and milk addition to beverages independently improved mood and reduced anxiety 30 and 60 min post-consumption. Milk addition had no other effects apart from attenuating the transient increase in physiological responses associated with the drinking phase. There were no effects of beverage consumption on salivary cortisol or of beverage vehicle on salivary caffeine levels, the latter indicating that caffeine pharmacokinetics was similar in both tea and coffee, and not different from caffeinated water. In keeping with this, the responses to tea and coffee ingestion were similar and largely accounted for by the effects of hot water and caffeine. However, tea potentiated the increase in skin temperature compared to coffee and water indicative of a greater vasodilatory response plausibly related to the presence of flavonoids in tea. We conclude that ingestion of hot caffeinated beverages stimulates physiological processes faster than hitherto described, primarily via the effects of hot water and caffeine, but with beverage type and milk playing important modulatory roles.

In acute dependence, signs and symptoms of opioid withdrawal are precipitated when an opioid antagonist (naloxone) is administered following acute (e.g. single dose) pretreatment with a mu agonist. This study examined the influence of amount of previous opioid exposure, both immediate and remote, on intensity of precipitated withdrawal effects in an acute dependence model. Two groups of subjects, opioid abusers (n = 20) and nonabusers (n = 20), received either one 15 mg/70 kg IM morphine pretreatment or two such pretreatments spaced 24 h apart. Naloxone challenge (30 mg/70 kg) followed 4.33 h after the second pretreatment. There were clear effects of morphine pretreatment condition (single versus repeated 15 mg) on the intensity of precipitated withdrawal responses elicited by naloxone. More intense effects were seen after the repeated pretreatment, suggesting that physical dependence escalates with repeated opioid exposures spaced at appropriate intervals. Subjects with an opioid abuse history reported greater liking of agonist drug effects than did nonabusers, whereas nonabusers reported more sedating effects. However, an opioid abuse history did not influence the intensity of precipitated withdrawal symptoms and signs. The latter finding suggests that a previous opioid exposure history does not dramatically modulate initial stages of physical dependence development during subsequent opioid exposure episodes.

Subjects received acute doses of orally administered alcohol (0-1.0 g/kg) and intranasal cocaine (4-96 mg/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST performance, increased ratings of drunkenness, heart rate and skin temperature, and decreased blood pressure. Combining cocaine and alcohol attenuated the disruptions in DSST performance observed with alcohol alone, and either did not change or attenuated the improvements in performance observed with cocaine alone. Combining the drugs also attenuated effects observed with the drugs alone on skin temperature and, to a lesser extent, blood pressure. By contrast, drug combinations increased heart rate above levels observed when cocaine or alcohol were administered alone. Effects of the drug combinations on subject ratings were variable.

Cocaine (2 mg/kg) was given orally to 13 healthy volunteers and physiologic, subjective, attentional and performance effects were measured over a period of 4 h. Posner's reaction time paradigm measured the effects of cocaine on performance and on attention to visual cues. Cocaine increased heart rate, systolic blood pressure and pupil diameter and reduced skin temperature. Physiologic effects, subjective rating of intoxication, and cocaine levels in saliva peaked at approximately 75 min and returned to precocaine levels within 3 h. In contrast, a reaction time measure of performance speed on the visual attention task showed improvement for 4 h after cocaine. A measure of covert attention in the cocaine condition failed to show the improvement which occurred in the placebo condition. Less fatigue was reported 4 h after cocaine than after placebo. Cocaine users may experience the drug's stimulant effects considerably longer than the euphoriant effects.

We examined the effect of morphine pretreatment spacing on intensity of subsequent precipitated withdrawal response to test the hypothesis that withdrawal intensity would be inversely related to pretreatment spacing. Subjects were ten nondependent male volunteers who reported using opioids an average of 2.5 times per week. Three IM morphine injections (each 18 mg/70 kg) were administered during each of four experimental conditions. The experimental conditions involved spacing injections at 12-, 24-, 48- or 72-h intervals. Naloxone (10 mg/70 kg IM) was administered 24 h after the last morphine exposure. A comparison condition was included in which a naloxone challenge was given at 24 h following a single IM morphine pretreatment (18 mg/70 kg). Subject rated measures of symptoms and observer-rated measures of signs indicated that withdrawal intensity was inversely related to the morphine spacing interval and in particular that intensity of withdrawal precipitated after three pretreatments spaced at 12-h intervals was greater than that precipitated after a single morphine pretreatment. Physiological data supported a more intense withdrawal response in the 12-h spacing condition and provided evidence of overshoot on blood pressure and skin temperature measures. These findings are pertinent to the transition between acute and chronic physical dependence; they suggest that there is a temporal window during which repeated opioid administrations result in escalation of physical dependence but that dependence levels after widely spaced multiple exposures may be no greater than after a single exposure.

Subjects with a history of free-basing and smoking cocaine but no history of opiate injections were exposed to three sets of stimuli. They received cocaine-related stimuli in one session, opiate-related stimuli in a second session, and non-drug stimuli on a third occasion. Compared to the opiate and non-drug cues, the cocaine-related events caused reliable decreases in skin temperature and skin resistance, and reliable increases in heart rate, self-reported cocaine craving, and self-reported cocaine withdrawal. Furthermore, control subjects lacking a history of cocaine or opiate use failed to show such differential responding. These results suggest that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients. Such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles.

Repeated administration of opioid drugs results in tolerance, a lessening of the drug's effect. There is pre-clinical evidence suggesting a conditioning component to drug tolerance. In the present study, six former opiate dependent subjects received i.v. opiate either by un-signalled infusion or by signalled self-injection and the effects were compared with those of saline under double-blind conditions. The subjects' pre-injection rituals constitute a signal which reliably predict the appearance of the opiate. These rituals produced drug-opposite physiological responses which resulted in an attenuation of the effects of the drug. Thus, tolerance was observed when the subjects injected the opiate, but not when the same dose was received by un-signaled intravenous infusion. These results are consistent with a conditioning explanation for the observed drug tolerance.

The behavioral and physiological effects of intranasally administered cocaine (placebo, 48, 96 mg/70 kg) were examined in eight recreational cocaine users under controlled laboratory conditions. The 48 and 96 mg doses of cocaine significantly improved subjects' performance on the Digit Symbol Substitution Test above levels observed either prior to drug administration or when placebo was administered. These effects were discernible for up to 120 min after cocaine administration. Cocaine had no statistically significant effects on learning and performance of ten-response sequences. The 48 and 96 mg doses increased heart rate and blood pressure for up to 180 min, and increased subject ratings of drug effects and decreased skin temperature for 60-90 min after drug administration. Cocaine produced no significant effects on the electrocardiogram. To our knowledge, this is the first experimental demonstration that acutely administered cocaine can improve behavioral performance in rested subjects. In addition, the duration of cardiac effects in this study was longer than previously reported with intranasal cocaine, perhaps due to the concurrent behavioral testing.

Studies were undertaken to determine the effects of acute alterations in plasma glucose levels on the tail skin temperature (TST) response of morphine-dependent rats to naloxone-precipitated withdrawal. In morphine-dependent rats, treatment with dextrose at doses of 0.5 or 2.5 g/kg did not alter the normal 6.0 +/- 0.3 degrees C TST response to naloxone. However, treatment with 5, 10 or 20 g dextrose/kg, which increased plasma glucose to 250 mg/dl or greater, blocked the TST response during morphine withdrawal. In contrast, an IV injection of 2.5 IU insulin (Na-porcine)/kg, which reduced plasma glucose for 2 h, caused a delayed TST response of 4.7 +/- 0.4 degrees C in control rats and exaggerated the TST response normally observed in morphine-dependent rats treated with naloxone. Collectively, these data indicate that acute hyperglycemia can attenuate and hypoglycemia can enhance the skin vasodilation which accompanies precipitated morphine withdrawal. In view of our observation that naloxone-precipitated morphine withdrawal caused a marked increase in blood glucose, the sympathetic activation associated with opiate withdrawal may be intended to elevate blood glucose and thereby limit the manifestation of the withdrawal response.

Conditioned heart rate and skin temperature responses of 12 social drinkers were observed following repeated exposure to alcohol. Each subject received alcohol for four sessions in one room and a non-alcoholic drink for four sessions in a room of quite different appearance. Alcoholic and non-alcoholic drinks were distinctive and the alcoholic content could not be determined on the basis of taste. In the final three testing sessions, placebos were presented in order to test the influence of room and drink cues separately and in combination. A conditioned heart rate response opposite in direction to the alcohol effect was elicited by room and drink cues in combination and by the room cue in isolation. These results were in accordance with the predictions of the conditioning model of tolerance. A conditioned heart rate response in the same direction as the drug effect was elicited by the drink cue presented in isolation. Similar, but non-significant changes were also obtained with skin temperature. In addition, conditioned responses occurred independently of any expectancy. The results demonstrated that the direction of conditioned drug responses may depend on the type of stimulus presented.

The beta-carboline ZK 93,426, a benzodiazepine receptor antagonist, was administered intravenously to human volunteers at two different doses (0.01 mg/kg, 0.04 mg/kg) according to a double-blind, placebo controlled design. Vital functions (i.e. blood pressure, heart rate, ECG, EEG), peripheral (finger) skin temperature and performance in psychometric tests for psychotropic and cognitive effects were evaluated. Blood samples were collected in addition and certain pharmacokinetic parameters were estimated. ZK 93,426 in both doses was well tolerated and exhibited no side effects. A decrease in peripheral skin temperature and heart rate was observed. In a general estimation of behavioural changes, volunteers experienced a stimulant and activating effect of the drug. An improvement in performance was observed in two cognitive tasks, the "logical reasoning task" and "pictures differences task" which estimated concentration and attention, respectively. No effects were found in time estimation. Plasma levels 5 min after intravenous administration of ZK 93 426 were 16 +/- 10 ng/ml and 52 +/- 31 ng/ml for 0.01 mg/kg and 0.04 mg/kg, respectively. Total clearance was calculated as 46 +/- 22 ml/min/kg (0.04 mg/kg).

Diltiazem, a benzothiazepine calcium channel antagonist, was given to six healthy men as a single 60 mg oral dose 120 min before IV injection of cocaine (0.2 mg/kg) in a double-blind, placebo-controlled, two-session study. Diltiazem alone produced no significant effects. Cocaine increased blood pressure, heart rate, pupil size and subjective "high" ratings, and decreased skin temperature. Diltiazem pretreatment diminished the cocaine effect on skin temperature, but did not otherwise alter the response to cocaine. Calcium channel antagonists diminish the effects of cocaine in vitro and in animals. Dosage considerations may be critical because of the differential sensitivity of various tissues to calcium channel antagonists.

A prominent effect of ethanol is on rectal body temperature. The use of a rectal probe to measure temperature can be stressful to the subject, especially when used repeatedly. We now present data on the hypothermic effect of ethanol (0.5, 1.0, 3.0, 3.5, or 4.0 g/kg) on surface body temperature in rats as detected by infrared radiation. Ethanol produced significant decreases in nasal temperature that were significantly correlated with changes in rectal temperature. Ethanol (3.5 g/kg) also produced a significant reversal in nasal hypothermia 15 min postinjection that was detected only with the infrared method. This new method is very rapid, accurate, requires minimal handling and may, therefore, be less stressful than rectal measurement to the subject.

An autonomic response opposite in direction to the effect of alcohol (i.e., a conditioned compensatory response) was found in normal social drinkers given alcohol placebo. Seven males received placebo in a distinctive drinking room after receiving vodka and tonic in two sessions in the same room; seven more males received distilled water in three sessions in that room. The response to placebo, consisting of decreased pulse transit time and finger skin temperature, was antagonistic to alcohol. The results support the application of the classical conditioning model of alcoholism to humans.

Changes in smoking behavior in response to a change in marijuana potency were measured in marijuana users. A marijuana cigarette containing 1.2% or 3.9% tetrahydrocannabinol (THC) was smoked on separate days by ten experienced users. Puff volume, duration and number, interpuff interval, inhalation volume and duration were averaged for each cigarette. The high potency cigarettes were smoked with more puffs and longer interpuff intervals, but also with greater inhaled volumes of air, thereby diluting the marijuana smoke.

The effects of caffeine on autonomic activity were tested in 19 normal prepubertal boys. Subjects received placebo, 3 mg/kg, and 10 mg/kg caffeine in a random order (double blind) before three test sessions 48 h apart. Skin conductance (SC), heart rate (HR), and skin temperature (ST) were recorded during a rest period, a series of nonsignal tones, and a simple reaction time (RT) task. Caffeine increased the frequency of both spontaneous and elicited SC responses (SCR) under all conditions. Resting SC base level (SCL) was increased, and shorter SCR half recovery time also occurred in some periods. In contrast, caffeine decreased HR and motor activity at 3 mg/kg. Evidence of improved attention on caffeine was also obtained. The physiological effects are partially similar to the effects seen in clinical anxiety states, and they are also consistent with the physiological concomitants of good sustained attention. The profile of effects did not resemble those of dextroamphetamine in a similar population.