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Biomedical subjects

J H Jaffe

Publications and source records attributed to J H Jaffe.

At least 19 recordsLinked to original sources
PubMed1995

Reinforcing effects of triazolam in sedative abusers: correlation of drug liking and self-administration measures.

Six male subjects with histories of sedative abuse were allowed to orally self-administer a maximum of 18 color-coded triazolam and placebo capsules during daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval 10-min schedule in which triazolam and placebo were concurrently available as mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the six subjects. The two subjects who did not self-administer triazolam in preference to placebo also had lesser histories of drug dependence. Self-administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable over 7-10 days. Manipulations of triazolam dose (0.0312-0.25 mg) per capsule in two subjects showed that the number of capsules self-administered was inversely related to capsule dose. Subject ratings of drug liking obtained from experimenter-administered doses of triazolam were correlated with self-administration behavior occurring 1-7 days later. Of the subject ratings, next day ratings obtained on the day after dosing resulted in significant correlations whereas same day ratings obtained while subjects were under the influence of triazolam did not. These results have important implications for abuse liability prediction and suggest that next day ratings have greater predictive validity than measures collected while subjects are under the influence of benzodiazepines.

Adult↗
PubMed1995

Assessment of nalmefene glucuronide as a selective gut opioid antagonist.

Opioid use often causes troublesome constipation as a side-effect. Selective antagonism of the intestinal actions of opioids might be useful in the treatment of opioid-induced constipation. We tested the inactive metabolite of nalmefene, nalmefene glucuronide, which showed promise of gut selectivity in rodent models, by administering ascending doses in single-blind, placebo-controlled fashion to five methadone-maintained, opioid-dependent male volunteers. Assessment of whether systemic or gut-selective opioid antagonist effects occurred was measured by vital signs, pupillary diameter, opioid withdrawal symptom scales, and bowel function. Oral nalmefene glucuronide precipitated symptoms and signs consistent with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after dosing. We conclude that nalmefene glucuronide does not appear to exert sufficient gut selectivity to be useful in antagonizing constipation due to exogenous opioid administration without antagonizing systemic opioid effects.

Adult↗
PubMed1993

Housing conditions influence acquisition of sufentanil aerosol self-administration in rats.

At weaning, rats were housed either individually or in pairs and as adults were trained to poke their nose in and out of a port that dispensed a 2-s exposure of sufentanil aerosol (50-micrograms/ml solution). During the acquisition phase, which consisted of five nightly sessions lasting 14-16 h, individually caged rats responded for more sufentanil aerosol than did pair-caged animals when the fixed ratio (FR) requirement was gradually increased from FR 1 to FR 5 over the five sessions. During the maintenance phase, which consisted of daytime 2-h sessions at an FR 5 schedule of reinforcement, there were no differences between individually and pair-caged animals responding for sufentanil or for water vapor. Both groups responded significantly more for sufentanil than for water vapor. Based upon present evidence, it is suggested that environmental and biologic determinants may change psychomotor behavior in a way that could influence the rate by which animals acquire drug-seeking behavior.

Aerosols↗
PubMed1993

Drug users' self-reports of behaviors and affective states under the influence of alcohol.

This study tested a modified version of the Alcohol-Related Behavior Questionnaire (ARBQ) to investigate the influence of alcohol on negative mood states. The ARBQ asked subjects (substance users and those not misusing drugs or alcohol) to recall various moods and behaviors under three drug conditions: sober, drinking, and drunk. Tests of the ARBQ subscales provided support for its reliability and validity. Scale scores measuring negative affect increased as levels of recalled alcohol intake increased, suggesting that larger amounts of alcohol produced more negative and aggressive feelings. Alcohol-dependent subjects reported more anger and aggression with increasing levels of alcohol intake than nonproblem drinkers. These data further indicated that, among those with alcohol dependence, a history of childhood aggression is an important predictor of negative behaviors and feelings associated with alcohol intake. Among other groups of drug users, a diagnosis of antisocial personality was relatively more important.

Adult↗
PubMed1992

A controlled trial of buprenorphine treatment for opioid dependence.

OBJECTIVE: To assess the efficacy of buprenorphine for short-term maintenance/detoxification. DESIGN: A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase. SETTING: Outpatient facilities at the Addiction Research Center, Baltimore, Md. PATIENTS: One hundred sixty-two volunteers seeking treatment for opioid dependence. INTERVENTION: In addition to the medication, counseling using a relapse prevention model was offered but not required. PRIMARY OUTCOME MEASURES: Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence. RESULTS: Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups. CONCLUSIONS: Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.

Adult↗
PubMed1992

Carbamazepine produces nonspecific effects on cocaine self-administration in rats.

Anecdotal evidence in humans suggest that carbamazepine suppresses cocaine-induced rush and craving. Such claims are unsupported in controlled trials using a placebo control. In the present study, rats were trained to self-administer i.v. cocaine in daily 2-hr sessions in which every tenth lever press delivered 1 mg/kg cocaine. After responding was stable, they were injected before each session with the vehicle for 2 days followed by carbamazepine for 2 days. At a 7 mg/kg dose, carbamazepine was without effect, whereas 15 mg/kg suppressed responding for cocaine only on the second (day 4) day of carbamazepine treatment. With 4 consecutive days of treatment, carbamazepine (15 mg/kg) reduced cocaine-maintained responding slightly, but significantly. In another group of animals trained to lever-press for food reinforcement, carbamazepine (15 mg/kg) also significantly decreased the rate of responding, suggesting that the suppression of responding was not specific to cocaine-reinforced behavior.

Animals↗
PubMed1992

Supersensitivity to naloxone following acute morphine pretreatment in humans: behavioral, hormonal and physiological effects.

The effects of naloxone (10 mg/70 kg) given 6 h following acute exposure to morphine (4, 8, 16 mg/70 kg) were assessed in 5 opiate-abusing volunteers who were not physically dependent upon entering the study. Naloxone increased cortisol plasma levels more following morphine than placebo pretreatment. Naloxone reversed the effects of morphine on pupil diameter and oral temperature and decreased skin temperature as a function of morphine pretreatment. Subjects' ability to detect the effects of naloxone, their scores on an opiate-withdrawal questionnaire, and their visual-analog ratings of 'bad effects', 'chills', 'confused' and 'restlessness' increased when naloxone followed pretreatment with 8 and 16 mg, but not 4 mg, of morphine. Performance on the Digit Symbol Substitution Test was not discernibly affected under any of the dose conditions. Overall, results from the present study provide further evidence in humans that the administration of naloxone shortly following acute morphine pretreatment increases naloxone sensitivity, produces signs and symptoms typical of opiate withdrawal and that these effects are dependent on the dose of morphine administered.

Adult↗
PubMed1992

Neuroendocrine responses to a glucose challenge in substance users with high and low levels of aggression, impulsivity, and antisocial personality.

Plasma glucose concentrations, and plasma prolactin and cortisol responses to a 5-hour oral glucose tolerance test (OGTT) in 37 substance abusers, were examined to assess the relationship between varying degrees of antisocial personality, impulsivity, and aggressiveness and measures of endocrine function. Childhood and presenting aggression, impulsivity and antisocial personality features were evaluated by several self-report questionnaires. Those with high scores for psychopathic deviance (MMPI) differed in glucose levels following OGTT from those with low scores. Lower cortisol nadir levels were associated with higher scores on measures of antisocial personality and aggressiveness. Also, prolactin response to glucose was attenuated relative to baseline levels in the more antisocial and aggressive subjects. The results indicate that substance abusers with high levels of self-reported antisocial personality and aggressive behavior have altered neuroendocrine responses to glucose challenge, although there was no evidence of hypoglycemia. No one personality or behavioral trait, as measured by our test battery, more strongly predicted neuroendocrine responses to glucose administration. Thus, our data partially support other reports of altered neuroendocrine responses to stressful challenges in aggressive/antisocial individuals.

Adult↗
PubMed1992

Treatment of cocaine dependence in methadone maintenance clients: a pilot study comparing the efficacy of desipramine and amantadine.

We conducted a pilot study (N = 22) comparing the efficacy of desipramine and amantadine for treatment of cocaine dependence in methadone maintenance clients. The study which lasted 12 weeks, was double-blind, randomly assigned, and placebo-controlled. Subjects met DSM-III-R criteria for active cocaine dependence. All three groups' cocaine use, craving, and depressive symptoms declined significantly, but intergroup differences were not significant. Clients receiving desipramine were significantly more likely to remain in treatment and to be cocaine free at study completion. The results emphasize the importance of delivering comprehensive services to the cocaine user in methadone treatment. Further evaluations of these two medications as adjuncts in the treatment of cocaine dependence are needed.

Adolescent↗
PubMed1991

Discriminative stimulus effects of inhaled cocaine in squirrel monkeys.

Squirrel monkeys (N = 4) were trained with food reinforcement to press one of two levers after administration of IV cocaine (0.3 or 1.0 mg/kg) or the other lever after saline. After training, IV cocaine (0.03-3.0 mg/kg) produced dose-related increases in the percentage of responses on the cocaine lever (ED50 = 0.15 mg/kg). Cocaine delivered IM also produced dose-related increases in cocaine-appropriate responding (ED50 = 0.32 mg/kg), but was approximately half as potent as IV cocaine. Similar relative potency relations were obtained for decreases in response rates produced by cocaine. Prior to some sessions subjects were placed in a Plexiglas chamber and exposed for 60 s to cocaine vapor created with an ultrasonic nebulizer. Exposure to vapor from cocaine solutions (1.0-30.0 mg/ml) produced concentration-dependent increases in cocaine-appropriate responding and decreases in response rates. Exposure to vapor from a 30 mg/ml concentration produced virtually exclusive cocaine-appropriate responding. Concentration-effect curves for inhaled cocaine were similar to dose-effect curves obtained when cocaine was administered by the other routes. The time course of the minimally effective concentration of inhaled cocaine was compared to that of the minimally effective doses of systemically administered cocaine. Inhaled cocaine had a duration of action longer than IV cocaine. The results indicate that inhaled cocaine vapor has effects qualitatively similar to those of IV cocaine, and may have a duration of action longer than that of an IV cocaine dose producing a similar degree of drug-appropriate responding.

Administration, Inhalation↗