TY - JOUR
T1 - Influence of phendimetrazine maintenance on the reinforcing, subjective, performance, and physiological effects of intranasal cocaine
AU - Stoops, William W.
AU - Strickland, Justin C.
AU - Alcorn, Joseph L.
AU - Hays, Lon R.
AU - Rayapati, Abner O.
AU - Lile, Joshua A.
AU - Rush, Craig R.
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Rationale: No pharmacotherapies are approved for cocaine use disorder. Phendimetrazine, a prodrug of the monoamine-releaser phenmetrazine, attenuates the reinforcing effects of cocaine in preclinical models, has minimal abuse potential, and is safe when combined with cocaine. Objectives: This study determined the influence of phendimetrazine maintenance on the reinforcing effects of cocaine (i.e., choice to self-administer cocaine), along with the subjective, performance, and physiological effects of cocaine. We hypothesized that phendimetrazine would attenuate the reinforcing effects of cocaine. Methods: Twenty-nine subjects with cocaine use disorder completed this within-subject, inpatient study. The subjects were maintained on placebo and 210 mg phendimetrazine in a counterbalanced order. After at least 7 days of maintenance on the target dose, the subjects completed experimental sessions in which the effects of single doses of 0, 20, 40, and 80 mg of intranasal cocaine were determined. Results: Cocaine functioned as a reinforcer, producing significant dose-related increases in self-administration. Cocaine increased prototypic effects (e.g., ratings of stimulated and blood pressure). Phendimetrazine attenuated ratings on a select set of subjective outcomes (e.g., ratings of talkative/friendly), but failed to reduce the reinforcing effects of cocaine or a majority of positive subjective cocaine effects. Phendimetrazine increased heart rate, indicating a physiologically active dose was tested, but heart rate increases were not clinically significant. Conclusions: These results indicate that although phendimetrazine can safely be combined with cocaine, it does not attenuate the abuse-related effects of cocaine. It is unlikely, then, that phendimetrazine will be an effective standalone treatment for cocaine use disorder.
AB - Rationale: No pharmacotherapies are approved for cocaine use disorder. Phendimetrazine, a prodrug of the monoamine-releaser phenmetrazine, attenuates the reinforcing effects of cocaine in preclinical models, has minimal abuse potential, and is safe when combined with cocaine. Objectives: This study determined the influence of phendimetrazine maintenance on the reinforcing effects of cocaine (i.e., choice to self-administer cocaine), along with the subjective, performance, and physiological effects of cocaine. We hypothesized that phendimetrazine would attenuate the reinforcing effects of cocaine. Methods: Twenty-nine subjects with cocaine use disorder completed this within-subject, inpatient study. The subjects were maintained on placebo and 210 mg phendimetrazine in a counterbalanced order. After at least 7 days of maintenance on the target dose, the subjects completed experimental sessions in which the effects of single doses of 0, 20, 40, and 80 mg of intranasal cocaine were determined. Results: Cocaine functioned as a reinforcer, producing significant dose-related increases in self-administration. Cocaine increased prototypic effects (e.g., ratings of stimulated and blood pressure). Phendimetrazine attenuated ratings on a select set of subjective outcomes (e.g., ratings of talkative/friendly), but failed to reduce the reinforcing effects of cocaine or a majority of positive subjective cocaine effects. Phendimetrazine increased heart rate, indicating a physiologically active dose was tested, but heart rate increases were not clinically significant. Conclusions: These results indicate that although phendimetrazine can safely be combined with cocaine, it does not attenuate the abuse-related effects of cocaine. It is unlikely, then, that phendimetrazine will be an effective standalone treatment for cocaine use disorder.
KW - Behavioral economic demand
KW - Cocaine
KW - Humans
KW - Pharmacotherapy
KW - Phendimetrazine
KW - Self-administration
UR - http://www.scopus.com/inward/record.url?scp=85063196665&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063196665&partnerID=8YFLogxK
U2 - 10.1007/s00213-019-05227-x
DO - 10.1007/s00213-019-05227-x
M3 - Article
C2 - 30900008
AN - SCOPUS:85063196665
SN - 0033-3158
VL - 236
SP - 2569
EP - 2577
JO - Psychopharmacology
JF - Psychopharmacology
IS - 9
ER -