Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans

Richard A. Nelson, Susan J. Boyd, Roy C. Ziegelstein, Ronald Herning, Jean L. Cadet, Jack E. Henningfield, Charles R. Schuster, Carlo Contoreggi, David A. Gorelick

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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 1 h 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.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalDrug and alcohol dependence
Issue number1
StatePublished - Mar 15 2006


  • Cardiovascular
  • Cocaine
  • Infusion rate
  • Subjective

ASJC Scopus subject areas

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


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