Repeated dosing with oral cocaine in humans: assessment of direct effects, withdrawal, and pharmacokinetics.
Exp Clin Psychopharmacol
; 17(4): 205-16, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19653786
ABSTRACT
Cocaine withdrawal symptoms are thought to play a role in relapse; studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a repeated-dosing, single-blind design in which subjects (n = 9), resided for 40 days on a closed ward. They were maintained for two 4-day cocaine exposure periods (Days 1-4 & Days 9-12, cocaine 175 mg, p.o.; 5 hourly doses; 875 mg/day) separated by a 4-day matched placebo exposure period (Days 5-8). After these 12 days, an additional period of 28 days of placebo maintenance followed (Days 13-40). Test sessions were conducted during each phase; measures of mood, drug effects, sleep, pharmacokinetics, and prolactin were collected throughout the study. The dosing regimen produced cocaine plasma concentrations (Cmax of 680 ng/mL) two to threefold higher than typically seen in acute dose studies. Prototypic psychostimulant effects, including subjective ratings of euphoric effects (liking, high, good effects) and significant cardiopressor effects, were sustained during the active dosing periods, corresponding to the rise and fall of plasma cocaine. Withdrawal-like symptoms (i.e., disruptions of sleep, increased ratings of anxiety, irritability, crashing) were observed within 24-hr after cessation of dosing. Cocaine reduced prolactin acutely, but no sustained alterations were observed for this measure or for other signs or symptoms during the 28-day abstinence period. These findings indicate that exposure to controlled high doses of cocaine produces modest symptoms consistent with cocaine withdrawal within hours of cessation of dosing but provide no evidence of symptoms persisting beyond 24 hours.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
/
Cocaína
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Exp Clin Psychopharmacol
Assunto da revista:
PSICOFARMACOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos