Department of Psychiatry, Connecticut V.A. Healthcare System and Yale University School of Medicine, West Haven, Connecticut 06516, USA
Abuse of illicit substances, in particular psychostimulants
and opiates, is a worldwide public health issue. Chronic use
of cocaine and amphetamine causes common neurobiological adaptations
that may guide new treatment development. These include perturbations
in dopamine and serotonin neurotransmission, leading to trials
of antidepressants, and serotonin and dopamine augmentation
strategies. The detection of cerebral perfusion abnormalities
caused by psychostimulants has led to examination of antiplatelet
and excitatory amino acid (EAA) antagonist therapies. Further,
development of cocaine vaccines allows for testing of peripheral
blockade approaches to cocaine addiction. New approaches to
behavioral treatments for cocaine dependence are also reviewed.
For opiate dependence, understanding of heroin's effects on
µ and
opiate receptors has led to investigations of the
partial µ agonist buprenorphine in opiate maintenance.
Evidence for hyper-excitability of locus coeruleus (LC) noradrenergic
neurons and EEA inputs to the LC guides trials of new
2-adrenergic
agonists and EEA antagonists to alleviate opiate withdrawal.
Finally, clinical experience with withdrawal from methadone
and LAAM has led to trials of antagonist-accelerated opiate
withdrawal. Improved treatment of psychostimulant and opiate
addiction is critically needed, and likely to have wide-reaching
impact in health care and society.
