Comparing the physiological and subjective effects of self-administered vs yoked cocaine in humans

Rationale: Studies with laboratory animals demonstrating different effects of self- vs experimenter-administered drug suggest that the ability to control or predict drug delivery may be an important determinant of drug action. Objective: This study assessed whether self-administered and yoked cocaine injections produce different effects in humans. Methods: Ten inpatient volunteers with experience in using cocaine participated in a double-blind, yoked design during which four experimental test sessions were conducted. During two sessions, participants controlled if and when up to six 40 mg/70 kg i.v. cocaine injections were given. During two sessions, participants received noncontingent exposure to the same pattern of injections given during the preceding session (i.e., yoked) under blind conditions. Sessions followed a fixed-order, ABAB design. Measures of subjective and physiological response to cocaine were taken throughout each session. Results: Cardiovascular safety parameters were exceeded in some individuals after yoked, but not self-administered, cocaine resulting in some scheduled injections being delayed or withheld. Mean systolic and diastolic blood pressures were higher following yoked compared to self-administered cocaine. In contrast, analysis of the subjective effects revealed only small and generally nonsignificant differences in the effects of self-administered vs yoked cocaine. Conclusions: These results suggest that under the laboratory methods employed, control over the schedule of drug delivery may not alter the subjective effects of cocaine in humans. In contrast, the cardiovascular effects of cocaine appear to be greater when the drug is administered noncontingently.