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Acute tolerance to cocaine in humans
J J Ambre1, S M Belknap, J Nelson
1Department of Medicine, Northwestern University Medical School, Chicago, IL.
Clinical Pharmacology and Therapeutics
|July 1, 1988
Summary
This study shows that acute tolerance develops to cocaine's effects in humans. Despite constant drug levels, subjective and heart rate effects diminish over time.
Area of Science:
- Pharmacology
- Neuroscience
- Human Physiology
Background:
- Controversy exists regarding acute tolerance to cocaine's primary effects in humans.
- Understanding tolerance is crucial for managing cocaine use and its health consequences.
Purpose of the Study:
- To investigate the development, rate, and extent of acute tolerance to cocaine's chronotropic and subjective effects.
- To quantify the relationship between plasma cocaine levels and physiological/subjective responses over time.
Main Methods:
- Administered intravenous cocaine injections followed by maintenance infusions in volunteer users.
- Maintained stable plasma cocaine concentrations to isolate tolerance effects.
- Monitored chronotropic (heart rate) and subjective (euphoric) effects.
Main Results:
- Subjective euphoric effects peaked at 1 hour and declined despite constant plasma cocaine levels.
- Chronotropic effects peaked within 10 minutes, then declined with a half-life of approximately 31 minutes.
- Tolerance development was modeled as an exponential process, altering the cocaine concentration-effect relationship.
Conclusions:
- Acute tolerance demonstrably develops to both the subjective and chronotropic effects of cocaine in humans.
- This tolerance develops rapidly and significantly impacts the perceived effects of the drug.
- Findings provide quantitative insights into the pharmacodynamics of acute cocaine tolerance.