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Biomedical subjects

M L Stitzer

Publications and source records attributed to M L Stitzer.

At least 109 records · Page 6Linked to original sources

Conditioned opponent responses: effects of placebo challenge in alcoholic subjects.

The present study continues a series of studies examining a number of variables that contribute to the demonstration of conditioned responses to alcohol in alcoholics. We pursued here the hypothesis that subjects receiving placebo in an environment previously associated with alcohol ingestion would exhibit conditioned responses as compared with subjects who had only received placebo in the environment. Further, we predicted that these conditioned responses would be opposite in direction to responses obtained during active drink sessions. Twelve subjects received active alcohol during session Days 1 through 4 and a placebo challenge on Day 5; the second group received placebo throughout sessions 1 through 5. On Day 1, heart rate and skin conductance were elevated following active alcohol ingestion as compared with placebo. On Day 5 following the placebo challenge, these physiological responses were significantly lower in the alcohol group as compared with the placebo group; the reversal of effects on Day 5 is suggestive of conditioned compensatory responses. Also, following the placebo on Day 5, desire to drink scores of the alcohol group were greater than those of the placebo group. The present data suggest that subjects exhibit conditioned compensatory responses when the environment signals alcohol availability. Results are consistent with Siegel's model of conditioned compensatory responses to repeated drug administration, and may help to account for some aspects of tolerance development and conditioned withdrawal.

Adult↗

Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval. I.

Acute opioid physical dependence refers to the withdrawal symptoms precipitated by an opioid antagonist administered after a single dose or short-term infusion of an opioid agonist. This phenomenon is particularly interesting given that the abstinence syndrome has generally been thought to develop only after chronic exposure to opioid agonists. The purpose of this study was to determine the minimum time after agonist administration when antagonist-precipitated withdrawal could be observed. Naloxone (10 mg/70 kg) was administered i.m. either 0, 15, 45 or 90 min after single i.m. injections of morphine (18 mg/70 kg) in five nondependent male opiate users. Physiological and subjective report measures revealed no effect of morphine or naloxone at the 0 and 15 min morphine-naloxone interval conditions; however, before the naloxone challenge 45 and 90 min post-morphine, agonist effects (e.g., miosis, respiratory depression and good drug effect subjective ratings) were clearly evident. Naloxone reversed these effects to premorphine levels and simultaneously precipitated subjective symptoms and observer rated signs of opiate withdrawal. Thus, this study showed that antagonist-precipitated withdrawal in humans was first observed 45 min after agonist administration. Further, the onset of naloxone-precipitated withdrawal effects closely paralleled the onset of morphine agonist effects. The results of this study suggest that adaptational changes underlying the development of physical dependence begin within minutes after acute exposure to an opiate.

Humans↗

Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure.

Antagonist-precipitated withdrawal after acute opioid administration (acute physical dependence) is an interesting phenomenon in that the opioid abstinence syndrome is generally thought to develop only after prolonged exposure to opioid agonists. The purpose of this study was to examine further this phenomenon in humans by characterizing the antagonist dose-response function. The effects of i.m. naloxone (0, 0.1, 0.3, 1, 3, 10 and 30 mg/70 kg) were assessed 6 hr after single i.m. injections of morphine (18 or 30 mg/70 kg) in six subjects with a history of chronic opiate use. Naloxone reversed residual morphine effects, including miosis and respiratory depression. The degree of reversal was dose-related to 10 mg/70 kg of naloxone with no further increases at the highest naloxone dose. Simultaneously, observer ratings of withdrawal signs and subjective reports of withdrawal symptoms were increased in an orderly dose-related manner to 30 mg/70 kg of naloxone. Reversal of residual morphine effects and onset of precipitated withdrawal were evident by 5-min postnaloxone; peak effects occurred within 15 min. This study confirmed the occurrence of antagonist-precipitated withdrawal after brief opioid exposure in humans, demonstrated the rapid onset of withdrawal effects and characterized the naloxone dose-response function.

Adult↗

Effects of alcohol on speaking in isolated humans.

Drugs of abuse often increase human social interaction, as is suggested in our cultural drug use practices and has been demonstrated in controlled laboratory studies. The environmental and pharmacological mechanisms controlling these effects remain unclear. The present study examined the importance of a social context for obtaining drug-produced increases in human speech by examining the acute effects of alcohol (0, 22, 45, 67 g) on the amount of speech emitted by six normal volunteers who were producing speech monologues in an isolated context. A within-subject repeated-measures experimental design was used. Alcohol produced a significant dose-dependent increase in total speech. Conversely, response rates on a nonverbal behavioral task (circular-lights device) decreased as an orderly function of alcohol dose. These results suggest that a social context is not a necessary condition for alcohol to increase rates of human speech. Moreover, the decreases in response rates observed in the nonverbal task rule out the possibility that alcohol affected total speech via a generalized increase in overall activity levels.

Adult↗

Alcohol and marijuana: comparative dose effect profiles in humans.

This study compared subjective and performance dose effect profiles of oral alcohol and smoked marijuana. Male subjects (N = 6) with histories of moderate alcohol and marijuana use received three doses of alcohol (0, 0.6, 1.2 g/kg) and three doses of marijuana (0, 1.3, 2.7% delta 9-THC) in a double-blind, randomized crossover design. Physiological indices indicated that active drug was delivered to subjects dose dependently. Alcohol produced dose-related elevations on several subjective measures of drug effect. The high dose of alcohol impaired performance on circular lights, tracking and digit-symbol substitution (DSST) tasks, whereas the low alcohol dose impaired only circular lights performance. Marijuana produced elevations on subjective report measures, but effects were similar for the two active doses. Minimal performance impairment was seen with marijuana on only one measure (DSST speed). The subjective and performance effect profiles produced by smoked marijuana were similar to that of the low (0.6 g/kg) dose of alcohol. These data are useful for understanding the relative performance impairment produced by alcohol and marijuana and the relationship between their subjective and behavioral effects.

Adult↗

Carbon monoxide exposure from commercial brand cigarettes under controlled smoking conditions.

Carbon monoxide (CO) exposure from ultralow-, low- and high-CO delivery commercial cigarettes was examined under controlled smoking conditions. Seven chronic smokers of mid- to high-CO delivery commercial cigarettes served in the experiment. CO level increases of 2.10, 5.76 and 7.38 ppm were obtained from ultralow-yield (1.6 mg CO delivery), low-yield (5.9 mg CO delivery) and high-yield (14.3 mg CO delivery) cigarettes, respectively. Subjects achieved significantly higher increases in CO levels from both low- and high-yield cigarettes than from ultralow-yield cigarettes, but increased levels of CO from low- and high-yield cigarettes were not different from each other. The data suggest that degree of CO absorption by the lungs during a short period of time may limit increases in CO levels obtained from high-yield cigarettes.

Adult↗

Time allocation in a concurrent schedule of social interaction and monetary reinforcement: effects of d-amphetamine.

Two mutually exclusive options (socializing versus monetary reinforcement) were concurrently available to two normal volunteers during 60-min experimental sessions under controlled laboratory conditions. The amount of money available in the monetary option was adjusted for individual subjects during baseline conditions until subjects divided their time approximately evenly between a social option in which they could converse with another same-sex volunteer or a monetary option in which money was earned for sitting quietly in a private room. In both subjects studied, d-amphetamine (5-25 mg) increased the percent of time allocated to the social option and total seconds of speech. This effect occurred even though increases in the time allocated to the social option necessarily resulted in a forfeiture of monetary reinforcement. The present results provide the first empirical evidence, to our knowledge, that d-amphetamine can increase the relative reinforcing effects of social interaction.

Adult↗

Contingency management in methadone maintenance: effects of reinforcing and aversive consequences on illicit polydrug use.

Treatment outcomes were compared for an intervention emphasizing reinforcement for abstinence from illicit drug use and an alternative intervention which combined the same reinforcement contingencies with aversive consequences for unauthorized drug use. Sixteen polydrug abusing methadone maintenance patients were randomly assigned to one of two treatment groups. Both groups received the opportunity to take methadone doses away from the clinic (take-home dose) as reinforcement for submitting urines testing negative for illicit substances. A regular weekly take-home dose of methadone could be earned for every 2 weeks of verified abstinence from unauthorized drugs, up to a maximum of three take-home doses per week. The combined intervention group had an additional contingency which involved a reduction in methadone dose as an aversive consequence for submitting urine samples testing positive for illicit substances. Specifically, 10% of the patient's daily methadone dose was lost for each week in which two of three urines tested positive for illicit drugs. An examination of the urinalysis results indicated no between group differences. Overall, 8% of the 12-week baseline urinalysis results tested negative for illicit substances while 42% tested negative for unauthorized substances during the 20 weeks of treatment intervention. At the end of the intervention period, nine subjects remained in treatment with three patients in each group receiving at least once weekly take-home privileges. Of the seven subjects no longer in treatment, five were in the combined intervention group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts.

The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts.

Adult↗

Psychophysiological effects of oral ethanol in alcoholics and social drinkers.

The acute and extended effects of ethanol ingestion were examined in five alcoholic subjects, and five "social" drinkers. Six physiological and four subjective report measures were taken before, during and up to 90 min after the ingestion of ethanol in three doses and placebo. Findings showed that alcohol exerted significant dose-related physiological effects in the initial minutes of ingestion, and in extended analyses of physiological and subjective measures in both groups of drinkers. Alcoholics and social drinkers generally did not differ in their physiological responses to alcohol doses and placebo, while some evidence for tolerance to reported euphoric effects of alcohol in the alcoholic subjects was found. The possibility is raised that early physiological responses observed during ethanol ingestion may arise not only from pharmacological effects of the drink, but may also be evidence for conditional predrink responses.

Adult↗

Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans.

This study assessed the blockade of hydromorphone challenge effects (cumulative s.c. doses of 0, 6 and 18 mg) during chronic buprenorphine treatment of opioid dependent subjects. Buprenorphine was administered daily via the sublingual route in ascending doses of 2, 4, 8 and 16 mg. Hydromorphone challenges were conducted after 10 to 14 days of chronic administration of each buprenorphine dose and 24 h after the last buprenorphrine dose. Buprenorphrine itself only produced dose-related effects in respiration rate. While subjects were maintained on 2 mg of buprenorphine, the hydromorphone challenge produced dose-related changes in physiological and self-report measures. As the dose of buprenorphine was increased, hydromorphone effects on self-report measures were attenuated to a greater extent than was noted for pupil diameter. The results of this study confirm previous reports of buprenorphine blockade of opioid agonist effects in humans and extent those findings by demonstrating both a buprenorphine dose-effect function and a dissociation between the potency of buprenorphine's opioid blockade for self-report vs. physiological measures.

Adult↗

Acute physical dependence in man: effects of naloxone after brief morphine exposure.

This study assessed the effects of i.m. naloxone (10 mg) 6 hr after acute i.m. injections of morphine (0, 1, 3, 5.6, 10 and 17 mg). Naloxone reversed residual morphine-produced respiratory depression, miosis and subjective reports of drug "high." In addition, naloxone precipitated signs and symptoms characteristic of opioid withdrawal. Subjective report measures of "bad" drug effects and specific opioid withdrawal symptoms increased as a function of morphine pretreatment dose, as did observer-rated signs of withdrawal. Yawning was the most prominent observed sign, whereas yawning and irritability were the most consistently reported subjective symptoms. Peak withdrawal effects were seen within 15 min post-naloxone. The results of this study confirm previous reports of acute physical dependence in man and extend those findings by demonstrating a morphine dose-response function.

Adult↗

Cigarette brand-switching: effects on smoke exposure and smoking behavior.

This study examined the effects of cigarette yield (Federal Trade Commission-determined deliveries of nicotine, tar and CO) on both biological exposure to smoke constituents and smoking behaviors. Smokers (N = 10) of high-yield cigarettes were switched in random order among five different commercially available cigarette brands with nicotine yields of 0.1, 0.4, 0.7, 1.1 (altered brand) and 1.0 (usual brand) mg and smoked each cigarette type for 5 days while a wide variety of assessments were performed. Steady-state cotinine and CO levels were substantially lower after 5 days of smoking ultra-low yield cigarettes (cotinine, 152 ng/ml; CO, 25 ppm) than when smoking usual-brand high-yield cigarettes (cotinine, 252 ng/ml; CO, 38 ppm). Both CO and nicotine boost (acute exposure) were related to yield. However, relative between-yield differences in all nicotine and CO exposure measures were smaller than predicted from Federal Trade Commission yield ratings. Substantial yield-related alterations were observed in smoking behavior. Subjects smoked more cigarettes and took larger and more closely spaced puffs when smoking low- as compared with high-yield cigarettes. The amount of tobacco burned per day was similar across all yield conditions. However, filter vent-blocking of ultra-low yield cigarettes did not appear to occur on a consistent basis. Subjective reports indicated poor acceptability of lower-yield cigarettes. We conclude that switching to lower-yield cigarettes brings about substantial alterations in smoking behavior which are at least partially responsible for the observed biological compensation associated with these cigarettes.

Adult↗