“Despite our familiarity with ethanol, we have remarkably little insight into the mechanisms by which it reduces inhibition and anxiety, nor do we know much about how it produces signs of more severe intoxication” – so concluded a recent literature review into the science of alcohol intoxication.

Like most topics in neurobiology, scientists understand ethanol intoxication less thoroughly than they would like. The brain, unsurprisingly, is wildly complex, and ethanol presents its own challenges that make the researchers’ job even more problematic. As a result, one can scarcely find a paper on alcohol intoxication which does not feature that old mainstay of technical scientific writing: ‘poorly understood.’

Work by clinicians, psychiatrists, and pathologists have provided us with a decent idea of what happens in the brain in a ‘big picture’ sort of way. Imaging studies with techniques such as fMRI – which infers changes in blood flow within the brain – found that certain regions, such as the frontal lobes, cerebellum, and limbic system are particularly affected by ethanol, and post-mortem studies found that these same regions are especially susceptible to damage in the brains of alcoholics.

These conclusions offer pleasant armchair explanations for the symptoms of drunkenness: we typically associate the frontal lobes with decision-making processes, which may be why we lose inhibition when we drink. The cerebellum is important for balance and motor control, which may contribute to why we lose balance and coordination. The limbic system is important for memory and regulating emotions, which may be why people blackout and get emotional when they drink heavily. There are important caveats for these explanations, as the brain is a dynamic, interconnected, and poorly understood organ.

This is not to say that large scale studies such as these are just hand-waving. Researchers have come up with detailed explanations and devised clever ways to test them. One such idea is the ‘Buoyancy Hypothesis,’ which seeks to explain the head-spinning vertigo that comes with inebriation through the structure of the inner ear. The semi-circular canals – three hollow, horseshoe-shaped bony chambers – play a central role in your perception of balance. The fluid that fills these chambers, endolymph, moves more slowly than the bony chamber. This difference in speed deflects a sensory organ (the cupula), generating a nervous signal that the brain uses to infer position and acceleration. According to this hypothesis, ethanol seeps into the cupula. Because ethanol is less dense than endolymph, the cupula starts to float, which throws the whole system into disarray. Some believe that the spinning gets worse when you close your eyes – possibly because visual stimuli can no longer counter the aberrant signaling from the inner ear. It’s a fun hypothesis and there is experimental evidence supporting this being at least part of the explanation.

However, researchers who look closer in order to study ethanol’s effects on a molecular and cellular level run into a host of problems all their own. For instance, ethanol’s pharmacology makes for challenging research. It is a tiny, simple molecule, meaning that there has to be a lot of it in your system for you to feel its effects, orders of magnitude higher than most other drugs and pharmaceuticals. Furthermore, ethanol’s small size means it can and does get everywhere in your body – every organ, every cell, every sub-cellular compartment. It also interacts with many, many proteins. According to one review, genetics screens have implicated more than one hundred different proteins in alcohol’s various effects. Because you need lots of ethanol to see an effect and because it gets everywhere and interacts with so many proteins, scientists have a hell of a time identifying direct protein targets of ethanol (the starting points for ethanol’s complex effects on the brain).

Despite these challenges, many researchers have pressed on with efforts to understand the short term effects of alcohol intoxication, typically in the hope of countering its unfortunate corollary – addiction. From the tangled science of ethanol’s molecular interactions, researchers have been steadily whittling down the list of candidate targets and building evidence to implicate certain molecules, sort out what these molecules have in common structurally and even pin down the roles of individual amino acids, the subunits that link together to form a protein. Many of these candidate molecules – such as GABAA receptors, NMDA receptors, and the BK channel – play important roles in the brain’s delicate electrical signaling. Other research has found roles for specific cell types, networks, and systems within the brain.

There is still, however, much work to be done. The picture is taking shape, but it is far from complete. So if you drink a bit too much this Christmas and don’t know what happened the night before, take solace in knowing the scientific community doesn’t know all the details either.