Are we dependent upon coffee and caffeine?
A review on human and animal
data
by
Nehlig A
INSERM U 398,
Faculte de Medecine,
Strasbourg,
France.
Neurosci Biobehav Rev 1999 Mar; 23(4):563-76
ABSTRACT
Caffeine is the most widely used psychoactive substance
and has been considered occasionally as a drug of abuse. The present paper
reviews available data on caffeine dependence, tolerance, reinforcement
and withdrawal. After sudden caffeine cessation, withdrawal symptoms develop
in a small portion of the population but are moderate and transient. Tolerance
to caffeine-induced stimulation of locomotor activity has been shown in
animals. In humans, tolerance to some subjective effects of caffeine seems
to occur, but most of the time complete tolerance to many effects of caffeine
on the central nervous system does not occur. In animals, caffeine can act
as a reinforcer, but only in a more limited range of conditions than with
classical drugs of dependence. In humans, the reinforcing stimuli functions
of caffeine are limited to low or rather moderate doses while high doses
are usually avoided. The classical drugs of abuse lead to quite specific
increases in cerebral functional activity and dopamine release in the shell
of the nucleus accumbens, the key structure for reward, motivation and addiction.
However, caffeine doses that reflect the daily human consumption, do not
induce a release of dopamine in the shell of the nucleus accumbens but lead
to a release of dopamine in the prefrontal cortex, which is consistent with
caffeine reinforcing properties. Moreover, caffeine increases glucose utilization
in the shell of the nucleus accumbens only at rather high doses that stimulate
most brain structures, non-specifically, and likely reflect the side effects
linked to high caffeine ingestion. That dose is also 5-10-fold higher than
the one necessary to stimulate the caudate nucleus, which mediates motor
activity and the structures regulating the sleep-wake cycle, the two functions
the most sensitive to caffeine. In conclusion, it appears that although
caffeine fulfils some of the criteria for drug dependence and shares with
amphetamines and cocaine a certain specificity of action on the cerebral
dopaminergic system, the methylxanthine does not act on the dopaminergic
structures related to reward, motivation and addiction.
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