Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans

Michelle R. Lofwall, Paul A. Nuzzo, Charles Campbell, Sharon L. Walsh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Aripiprazole is a partial agonist at dopamine (D2) and serotonin (5-HT1a) receptors and 5-HT2 antagonist. Because cocaine affects dopamine and serotonin, this study assessed whether aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole on ad lib cigarette smoking and with a novel 40-hr smoking abstinence procedure. Adults with regular cocaine and cigarette use completed this inpatient double blind, randomized, placebo-controlled mixed-design study. A placebo lead-in was followed by randomization to aripiprazole (0, 2 or 10 mg/day/p.o.; n = 7 completed/group). Three sets of test sessions, each consisting of 3 cocaine sample-choice (i.e., self-administration) sessions and 1 dose-response session, were conducted (once during the lead-in and twice after randomization). Sample sessions tested each cocaine dose (0, 20 and 40 mg/70 kg, i.v.) in random order; subjective, observer-rated and physiologic outcomes were collected. Later that day, participants chose between the morning's sample dose or descending amounts of money over 7 trials. In dose response sessions, all doses were given 1 hr apart in ascending order for pharmacodynamic and pharmacokinetic assessment. Two sets of smoking topography sessions were conducted during the lead-in and after randomization; 1 with and 1 without 40 hr of smoking abstinence. Number of ad lib cigarettes smoked during non-session days was collected. Cocaine produced prototypic effects, but aripiprazole did not significantly alter these effects or smoking outcomes. The smoking abstinence procedure reliably produced nicotine withdrawal and craving and increased smoking modestly. These data do not support further investigation of aripiprazole for cocaine or tobacco use disorder treatment.

Original languageEnglish (US)
Pages (from-to)238-247
Number of pages10
JournalExperimental and Clinical Psychopharmacology
Volume22
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Self Administration
Cocaine
Smoking
Random Allocation
Tobacco Products
Placebos
Serotonin 5-HT2 Receptor Antagonists
Tobacco Use Disorder
Receptor, Serotonin, 5-HT1A
Dopamine Agonists
Aripiprazole
Nicotine
Inpatients
Dopamine
Serotonin
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans. / Lofwall, Michelle R.; Nuzzo, Paul A.; Campbell, Charles; Walsh, Sharon L.

In: Experimental and Clinical Psychopharmacology, Vol. 22, No. 3, 01.01.2014, p. 238-247.

Research output: Contribution to journalArticle

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