The University of Arizona

History, Pharmacology, and Prevalence
Cocaine Overview:


In general, cocaine acts by blocking the reuptake of neurotransmitters, such as norepinephrine, dopamine, and serotonin, at the synaptic junction.  As a result, there is an accumulation of neurotransmitters causing continuous stimulation that leads to the pleasurable effects reported by cocaine users.[1-3]  These effects include feelings of euphoria which are associated with the excess presence of dopamine, feelings of confidence which are associated with the excess presence of serotonin, and feelings of energy which are associated with the excess presence of norepinephrine.[4]  The neural system most affected by cocaine is called the ventral tegmental area (VTA) [2], which is central to positive reinforcement aspects of addiction.[5,6] 
Click here to see an animation on how cocaine works in the brain.

Timing of Effects

As with methamphetamine, cocaine’s fastest routes into cerebral circulation are smoking and injecting, which take a matter of only seconds.[1,3,7,8]  In comparison, euphoria occurs one to five minutes after cocaine is snorted.[3]  Smoking and injecting cocaine produces a rush and then a high, whereas snorting cocaine produces only a high.[7]  This is due in part to the fact that the amount of cocaine absorbed in the nasal mucosa has bioavailability of only 20 to 60%, whereas the bioavailability of, for example, smoked cocaine is approximately 70%.[1,9]  Also, snorting cocaine causes local vasoconstriction, therefore inhibiting faster absorption.[8]


Benzoylecgonine and ecgonine methyl ester are the two inactive metabolites that account for more than 80% of cocaine’s known metabolites.  The liver N-demethylates less than 10% of cocaine into a toxic metabolite called norcocaine.[1,3,8]  Regardless of the route of administration, cocaine and its metabolites present themselves in urine three to six hours after use.[8]  With a half-life of about one hour, less than 5% of cocaine appears in urine unchanged. As a result, benzoylecgonine is the major metabolite used in drug testing since its concentration in urine is 50 to 100 times greater than that of cocaine.[1,8]

Local Anesthetic Properties

Cocaine prevents conduction of sensory impulses by reacting with the neuron membrane to block ion channels.  As a result of this block, the ion exchange which is normally responsible for the electrical signals cannot be propagated along the axon, and the sensory messages are not received in the central nervous system—hence the anesthetic effect.[10]



  • (1) Warner EA. Cocaine Abuse. Ann Intern Med 1993 Aug 1;119(3):226-35.
  • (2) NIDA. Cocaine: Abuse and Addiction. Rockville, MD; 2004 Nov. Report No.: 99-4342.
  • (3) Egred M, Davis GK. Cocaine and the heart. Postgraduate Medical Journal 2005 Sep 1;81(959):568-71.
  • (4) Canadian Institutes of Health Research. How Drugs Affect Neurotransmitters. Web 2007. Available from: URL:
  • (5) Kim H, Iyengar S, Wood P. Opiate actions on mesocortical dopamine metabolism in the rat. Life Sciences 1986;39(2033):2036.
  • (6) Masterman D, Cummings J. Frontal-subcortical circuits: The anatomic basis of executive, social, and motivated behaviors. Journal of Pscyhopharmacology 1997;11:99-106.
  • (7) Middleton PM. Cerebrovascular Effects of Cocaine. The Internet Journal of Emergency Medicine 2004;2(1).
  • (8) Shanti CM, Lucas CE. Cocaine and the critical care challenge. Criticial Care Medicine 2003 Jun;31(6):1851-9.
  • (9) Cone EJ. Recent discoveries in pharmacokinetics of drugs of abuse. Toxicology Letters 1998 Dec 28;102:97-101.
  • (10) Brown R. Pharmacology of Cocaine Abuse. In: Redda K, Walker C, Barnett G, editors. Cocaine, Marijuana, Designer Drugs: Chemistry, Pharmacology, and Behavior. 1989.


  • ="Brain
    Brain on Cocaine