Jerome H. Jaffe

Placebo responses to cocaine administration in humans: effects of prior administrations and verbal instructions

Subjective and physiological responses of eight male cocaine-using research volunteers were studied after a double-blind saline infusion (placebo) was given when subjects were instructed that a cocaine infusion might be given. Cardiovascular and subjective responses to placebo were similar in pattern and direction, though of lesser magnitude, than after a 40 mg cocaine infusion. These placebo responses were compared to responses after an earlier saline infusion condition in which subjects were instructed prior to the infusion that they would receive saline (instructed placebo). The design was thus meant to test for the effects of instructions on placebo responses to cocaine. Heart rates at baseline (pre-infusion) were significantly higher in the placebo than in the instructed placebo condition. Similar trends were found for elevated baseline placebo responses on two subjective effects measures. A comparison with an initial placebo session prior to the placebo and instructed placebo conditions described above provided evidence for conditioning of placebo responses on diastolic blood pressure and heart rate. The present results suggest that verbal instructions, as well as conditioning in the laboratory, could contribute to the observed placebo responses to cocaine infusions.

Effects of nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine in humans

The effects of oral nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine infusions were studied in cocaine-using volunteers. Nifedipine, 10 mg or placebo, was administered 20–25 min before placebo, 20 mg, or 40 mg cocaine, using a repeated measures randomized double-blind design. The variables measured were self-reported subjective effects, general behavior rated by two observers, blood pressure and heart rate. Cocaine produced the expected dose-related effects on subjective and cardiovascular measures. Nifedipine pretreatment attenuated some subjective effects of cocaine. Nifedipine directly reduced blood pressure but did not antagonize the effects of cocaine on blood pressure. These findings suggest that dihydropyridine calcium channel modulators may be useful compounds in the clinical management of cocaine users.

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.

Correlates of Self-Reported Early Childhood Aggression in Subjects Volunteering for Drug Studies

The construct validity of a retrospective self-report measure of early childhood aggression, the Early Experience Questionnaire (EEQ), was assessed in a sample of substance abusing volunteers for drug studies at a research center in Baltimore. In contrast to the diagnosis of Antisocial Personality Disorder (APD), EEQ scores were not only associated with adult aggression, criminality, and substance abuse, but were also highly correlated with a cluster of measures reflecting emotionally reactive impulsivity. Correlations of the EEQ with the Minnesota Multiphasic Personality Inventory confirmed earlier findings obtained on a sample of alcoholics. Over and above the predictive influence of APD, early childhood aggression had some predictive influence on the incidence and severity of substance abuse but a substantial influence on the prediction of criminality.

Intravenous cocaine infusions in humans: Dose responsivity and correlations of cardiovascular vs. subjective effects

Eight experienced IV cocaine users were intravenously administered 0, 10, 20, and 40 mg of cocaine hydrochloride on separate days in a pseudo-randomized ascending dose series, such that the 20 mg dose always preceded the 40 mg dose. They were subsequently administered 0, 20, and 40 mg of cocaine in a fully randomized presentation order. Cardiovascular effects of cocaine were significantly different from placebo for the 20 mg, but not the 10 mg dose, in contrast to subjective responses which differed from placebo for the 10 mg dose. Cardiovascular and subjective effects of cocaine did not differ between the 20 and 40 mg dose conditions for the pseudo-randomized trials, but did differ in the fully randomized trials. This lack of difference in responsivity between the 20 and 40 mg dose in the earlier trials may possibly have been due to contrast effects. Cardiovascular responses were not consistently correlated with subjective responses, either within a cocaine dose condition or across doses.

Self-report vs. laboratory measures of aggression as predictors of substance abuse

Measures of aggressive behavior, antisocial personality, criminality, and impulsivity were obtained on a sample of 85 drug abusing volunteers for studies at the Addiction Research Center in Baltimore. Measures included the Buss-Durkee Hostility Inventory, Diagnostic Interview Schedule Antisocial Personality Disorder diagnosis, Elliott-Huizinga Lifetime Events Scale, Eysencks Impulsiveness-Venturesomeness-Empathy scales, and a laboratory measure of aggression patterned after the Buss aggression machine. All of the self-report measures of aggression and antisocial personality were moderately correlated with each other, but did not correlate with the laboratory aggression measure. This laboratory measure, nevertheless, made a significant contribution to the prediction of certain substance abuse diagnoses over and above the contributions of the other measures.

Cardiovascular responses to cocaine placebo in humans: A preliminary report

Cardiovascular responses after placebo-cocaine injections were in the same direction as the effect of cocaine iv in 22 male volunteers. Subjects received iv placebo in a room where they had been given repeated doses of iv cocaine. The placebo response consisted of an increase from baseline values of systolic and diastolic blood pressure and pulse rate. The control group, 8 subjects, which was not exposed to a conditioning phase, showed a smaller increase in the pulse rate and systolic blood pressure after the placebo injection. The results, in accordance with animal literature, suggest the existence of cocaine-conditioned effects in humans.