What receptor/NT imbalance characterizes benzodiazepine withdrawal?

Benzodiazepine withdrawal is characterized by a downregulation of GABA receptors and an upregulation of NMDA receptors. Benzodiazepines primarily work by enhancing the effect of the neurotransmitter GABA at the GABA-A receptor, leading to increased inhibitory activity in the central nervous system. During prolonged use, the body adapts to this enhanced inhibition, which can result in reduced sensitivity and/or number of GABA receptors, hence downregulation.

When benzodiazepine use is discontinued, this adaptation leads to a relative deficiency of GABA receptor activity, which can cause symptoms of increased excitability, anxiety, and seizures due to the unopposed action of excitatory neurotransmitters. Concurrently, there is an upregulation of NMDA receptors, a key player in excitatory neurotransmission, to counterbalance the increased inhibition. This shift towards increased excitatory activity manifests as significant withdrawal symptoms, making the imbalance between GABAergic inhibition and glutamatergic excitation a critical aspect of benzodiazepine withdrawal syndrome.

Maintaining a balanced state in GABA and NMDA receptor functions is not possible during withdrawal, as the body's neurochemistry is actively responding to the absence of the substance. Therefore, the