The British Journal of Psychiatry
Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal.
P Glue, D Nutt


In alcohol withdrawal, abnormalities occur in a number of neurotransmitter systems: there is reduced inhibitory function, and increased activity of excitatory systems. The former, indicated by reduced GABA and alpha-2-adrenoceptor activity, acts in conjunction with, and is exacerbated by, the latter, which itself may be due to the potentiation of NMDA activity by depletion of magnesium, and overactivity of catecholaminergic and CRF neurones. These dysfunctions produce immediate effects and may also contribute to the long-term changes in brain excitability by a kindling-like process. It is possible that early and active treatment may oppose this process. Present strategies for treatment of alcohol withdrawal enhance GABA and alpha-2 inhibitory, or reduce excitatory, mechanisms. Future possibilities include the use of CRF and/or NMDA antagonists.