title: Modafinil and cocaine: a double-blind, placebo-controlled drug interaction study.
abstract: Modafinil is a novel compound that is approved for the treatment of narcolepsy. It is now being studied as a potential treatment for cocaine dependence. Cocaine withdrawal symptoms are associated with poor clinical outcome and are likely to be reversed by modafinil. In addition, the neurotransmitter actions of modafinil are opposite to cocaine-induced neuroadaptations affecting dopamine and glutamate reward circuits. Since cocaine-dependent subjects might use cocaine during a clinical trial with modafinil, this study tested the safety of intravenous cocaine (30 mg) in combination with modafinil. Each of seven subjects received a baseline (open-label) cocaine infusion. Three subsequent cocaine infusions were administered after subjects received 4 days of low dose modafinil (200 mg/day), high dose modafinil (400 mg/day), or placebo in randomized double-blind sequences. One subject received placebo prior to all infusions. Our results indicate that co-administering modafinil and a single dose of intravenous cocaine is not associated with medical risk in terms of blood pressure, pulse, temperature, or electrocardiogram measures. Furthermore, pretreatment with modafinil did not intensify cocaine euphoria or cocaine-induced craving. In fact, cocaine euphoria was significantly blunted (P=0.02) in one of our subjective measures.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104, USA. dackis@mail.med.upenn.edu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dackis
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Lynch
authors.forename: Elmer
authors.initials: E
authors.lastname: Yu
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Samaha
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Kampman
authors.forename: James W
authors.initials: JW
authors.lastname: Cornish
authors.forename: Amy
authors.initials: A
authors.lastname: Rowan
authors.forename: Sabrina
authors.initials: S
authors.lastname: Poole
authors.forename: Lenae
authors.initials: L
authors.lastname: White
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003042:Cocaine / Q000009:adverse effects* / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D011674:Pulse
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D003042:Cocaine; D000077408:Modafinil