Stimulant dependence has become a major public health problem in the world over the last 15 years, and
pharmacotherapies have been evolved based on our understanding of the neurobiological alterations induced by these drugs. Among the stimulants
cocaine and
amphetamine are the most common dependencies, and they share several common pathophysiologies in producing disease and in guiding medication approaches to treatment--
neurotransmitter re-normalization, reversal of cerebral perfusion abnormalities and peripheral
cocaine blockers. First is
neurotransmitter re-normalization. A relative
catecholamine deficiency occurs following prolonged abuse of
cocaine and
amphetamine due to transporter upregulation and receptor downregulation. This abnormality in
dopamine and
serotonin neurotransmission appears to be associated with depression and has supported
antidepressant treatments to re-normalize neurotransmission. Dopaminergic and
serotonergic agonists have also been given to re-normalize neurotransmission, but in contrast to substitution
therapies such as
methadone,
LAAM or
buprenorphine for
opioids, these approaches have had limited success in unselected
cocaine dependent patients. As a correlary approach to substitution, however, aspects of
dopamine function can be augmented by
dopamine beta hydroxylase inhibitors such as
disulfiram to increase the aversive properties of stimulants and decrease their abuse. The second medication approach relates to cerebral perfusion defects and associated cognitive deficits due to vasoconstriction and abnormalities in platelets, which can respond to antiplatelet
therapies as well as
excitatory amino acid (
EAA) antagonists. These
EAA antagonists can prevent neuronal damage that is due to the release of EAA during
cerebral ischemia induced by stimulant use. Finally, peripheral blockade treatment for
cocaine may be possible using a newly developed active
vaccine that blocks the uptake of
cocaine from the bloodstream into the brain. Its potential efficacy has been shown in rodents that decrease their
self-administration of
cocaine when immunized with this
vaccine, and preliminary human studies support its safety and immunogenicity. In summary, stimulant
pharmacotherapy has made great progress in developing treatments based on understanding the neurobiology of these abused drugs, but these
pharmacotherapies must be delivered in the context of appropriate behavioral and cognitive psychotherapies, which are also rapidly evolving.