Acute tolerance to cocaine in humans

  title={Acute tolerance to cocaine in humans},
  author={John J. Ambre and Steven M. Belknap and John Nelson and Tsuen Ih Ruo and S‐G Shin and Arthur J. Jr. Atkinson},
  journal={Clinical Pharmacology \& Therapeutics},
There is controversy as to whether acute tolerance develops to the principal effects of cocaine in humans. The studies described here demonstrate the phenomenon of acute tolerance to cocaine chronotropic and subjective effects and the rate and extent of tolerance development. Stable plasma cocaine concentrations were produced and then maintained in volunteer cocaine users by administering an intravenous cocaine injection followed by a cocaine infusion designed to compensate for the plasma… 
Intranasal cocaine in humans: acute tolerance, cardiovascular and subjective effects
Subjective response during continuous infusion of cocaine
Cardiovascular effects of cocaine in humans: laboratory studies.
Tolerance to self-administration of cocaine in rats: time course and dose-response determination using a multi-dose method.
Acute and Chronic Dopamine Dynamics in a Nonhuman Primate Model of Recreational Cocaine Use
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It is demonstrated that recreational levels of cocaine consumption can result in neurochemical sensitization, an enduring change in brain function that may contribute to addiction, and the contrast in time-dependent changes in neuro chemical responsiveness to cocaine is highlighted.
Tolerance Develops to the Sympathomimetic But Not the Local Anesthetic Effects of Cocaine
At high doses, cocaine's local anesthetic properties predominate, become more pronounced with repeated administration, and may have implications for cocaine-related dysrhythmias, cardiovascular collapse, and sudden death.


Acute tolerance development to the cardiovascular and subjective effects of cocaine.
There is a decrease in physiological and subjective effects of cocaine when administered repeatedly in humans, and this acute tolerance appeared to have dissipated within 24 hr.
Kinetics of cocaine distribution, elimination, and chronotropic effects
The kinetic analysis demonstrated that the chronotropic effects of cocaine decline more rapidly than either plasma levels or biophase concentrations, and could be modeled as a first‐order process and is compatible with either the intervention of homeostatic reflex mechanisms or the phenomenon of acute tolerance.
Cocaine self-administration in humans.
The self-administration data and data describing the subjective and cardiovascular spectrum of action were combined to yield a more complete profile of cocaine's action in humans.
Urinary excretion of ecgonine methyl ester, a major metabolite of cocaine in humans.
The time course of ecgonine methyl ester excretion is such that its detection can substitute for benzoylecgonine detection as a marker of cocaine use, and these results indicate that Ecgonineethyl ester accounts for most of the previously unidentified urinary metabolic products of cocaine.
Kinetic Analysis of the Vasodilator and Ganglionic Blocking Actions of N‐Acetylprocainamide
The hypotensive effects of N-acetylprocainamide (NAPA) were studied in anesthetized dogs and in a normal subject, and results suggest that blood pressure should be monitored for at least 10 min after patients receive an intravenous NAPA injection, and that repeated N APA doses probably should not be administered more frequently.
Free‐base cocaine smoking
Six healthy male, paid subjects smoked 50 mg of free‐base cocaine in a specially designed glass pipe under a rigidly controlled smoking protocol and the cocaine free base inhaled induced psychological and cardiovascular effects similar to, or slightly more intense and pleasurable than, the effects of 20mg of cocaine HCl (18 mg of cocaine base) taken intravenously by the same subjects.
A new method for constant plasma drug concentrations: application to lidocaine.
A new simple method of delivering an infusion produces a delivery rate that declines exponentially, thereby providing stable plasma concentrations after a bolus dose, and has been tested both ex vivo and in normal volunteers receiving lidocaine.
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