Acute tolerance to cocaine in humans

Area of Science:

• Pharmacology
• Cardiovascular Science

Background:

• A dose-response relationship exists between intravenous cocaine levels and heart rate.
• Cardiovascular effects of inhaled cocaine diminish faster than plasma cocaine levels decrease.
• This suggests potential acute tolerance to cocaine's cardiovascular effects with repeated or sustained exposure.

Purpose of the Study:

• To investigate acute tolerance to cocaine's cardiovascular effects.
• To compare the effects of a second intravenous cocaine dose with and without a pre-existing blood level.

Main Methods:

• Administered cocaine via intranasal route to maintain sustained blood levels.
• Monitored heart rate changes in relation to cocaine blood levels.
• Compared the cardiovascular response to a subsequent intravenous cocaine dose in subjects with and without pre-existing cocaine blood levels.

Main Results:

• Intranasal administration allowed sustained cocaine blood levels.
• Heart rate decreased from peak levels despite maintained blood concentrations.
• The second intravenous dose produced a diminished cardiovascular response in subjects with pre-existing cocaine levels.

Conclusions:

• Evidence supports the development of acute tolerance to cocaine's cardiovascular effects.
• Sustained cocaine blood levels, achieved through intranasal administration, can lead to tolerance.
• This tolerance impacts the cardiovascular response to subsequent cocaine administration.