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Enhanced sensitivity to benzodiazepines in active cocaine-abusing subjects: a PET study
N D Volkow1, G J Wang, J S Fowler
1Medical Department, Brookhaven National Laboratory, NY 11973, USA. volkow@bnl.gov
The American Journal of Psychiatry
|February 17, 1998
Summary
Cocaine abusers show increased brain sensitivity to lorazepam, indicating disrupted gamma-aminobutyric acid (GABA) pathways. This heightened response may be linked to cocaine withdrawal and warrants clinical caution with sedative hypnotics.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Cocaine use elevates dopamine, influencing neurotransmitter systems.
- Dopamine pathways are interconnected with gamma-aminobutyric acid (GABA) neurotransmission.
- Previous research suggests potential GABA-ergic system alterations in substance abuse.
Purpose of the Study:
- To investigate potential disruptions in GABAergic pathways in individuals with current cocaine abuse.
- To test the hypothesis that cocaine abuse alters brain metabolic responses modulated by GABA.
Main Methods:
- Assessed GABA brain function indirectly by measuring metabolic response to lorazepam, a GABA facilitator.
- Utilized positron emission tomography (PET) with [18F]fluorodeoxyglucose to scan 13 cocaine abusers and 14 controls twice: after placebo and after lorazepam administration.
- Measured brain metabolism and subjective effects (sleepiness).
Main Results:
- Cocaine abusers exhibited significantly greater whole-brain metabolic reductions (21%) compared to controls (13%) after lorazepam, despite lower plasma lorazepam levels.
- Enhanced lorazepam effects were most pronounced in the striatum, thalamus, and parietal cortex.
- Cocaine abusers reported more intense sleepiness correlated with thalamic metabolic changes, and regional metabolism during lorazepam administration was similar between groups.
Conclusions:
- Heightened sensitivity to lorazepam in cocaine abusers suggests disrupted GABA pathways, potentially related to cocaine withdrawal.
- Clinicians should be aware of potential toxicity and accentuated responses to sedative hypnotics in active cocaine-abusing individuals due to enhanced sensitivity.