title: Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans.
abstract: The rate hypothesis of psychoactive drug action holds that the faster a drug reaches the brain and starts to act, the greater its reinforcing effects and abuse liability. A previous human study using a single cocaine dose confirmed the rate hypothesis for subjective responses, but found no rate effect on cardiovascular responses. We evaluated the rate hypothesis in 17 experienced cocaine users (7 [all men] provided complete data; 6 participated in only 1-2 sessions) by administering IV cocaine at each of three doses (10, 25, 50 mg) and injection durations (10, 30, 60 s) in a double-blind, placebo-controlled, escalating dose design. Heart rate, blood pressure, and positive (e.g., rush, high) and negative (e.g., feel bad, anxious) subjective effects (100-mm visual analogue scales) were measured for 1h after dosing. Peak change from baseline, time to peak, and area under the time-response curve were evaluated with repeated measures mixed linear regression analyses, allowing use of data from all sessions for all subjects, including non-completers. Both dose (mg) and infusion rate (mg/s) significantly influenced most subjective and cardiovascular variables. Analysis of the interaction suggested that dose had a stronger impact than rate. Rate had a stronger influence on positive subjective effects than on negative subjective effects or cardiovascular variables. These findings provide support for the rate hypothesis as it applies to both subjective and cardiovascular effects of IV cocaine administration in humans.
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health & Human Services, Baltimore, MD 21224, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nelson
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Boyd
authors.forename: Roy C
authors.initials: RC
authors.lastname: Ziegelstein
authors.forename: Ronald
authors.initials: R
authors.lastname: Herning
authors.forename: Jean L
authors.initials: JL
authors.lastname: Cadet
authors.forename: Jack E
authors.initials: JE
authors.lastname: Henningfield
authors.forename: Charles R
authors.initials: CR
authors.lastname: Schuster
authors.forename: Carlo
authors.initials: C
authors.lastname: Contoreggi
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
mesh_terms: D000328:Adult; D001007:Anxiety / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000453:epidemiology* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004569:Electroencephalography; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010507:Periodicity; D015995:Prevalence; D015819:Substance Abuse, Intravenous / Q000453:epidemiology* / Q000503:physiopathology*
chemical_list: D003042:Cocaine