Excitability

Excitability describes how close a neuron — or a region of cortex — sits to its firing threshold at any given moment. A highly excitable cell needs only a modest incoming signal to generate an action potential; a strongly inhibited one may ignore the same stimulus entirely.

This property is set by the ongoing balance between two competing forces: glutamate, the brain's primary excitatory transmitter, which pushes neurons toward firing, and GABA, the primary inhibitory transmitter, which pulls them back. The ratio of these two systems — the E/I balance — shifts continuously across brain regions, and changes substantially under different substances.

How it works · its role

At the cellular level, excitability reflects the neuron's resting membrane potential relative to its firing threshold. Excitatory inputs briefly depolarise the membrane, nudging voltage upward; inhibitory inputs hyperpolarise it, pushing voltage away. Whether a spike is generated depends on the sum of these competing signals at any given moment.

Excitability is also shaped by neuromodulators — dopamine, noradrenaline, acetylcholine, and others — which adjust the sensitivity of circuits without themselves triggering firing. This is why the same sensory input can feel sharp during high arousal and dull during sedation: excitability itself has shifted, not the stimulus.

Relevance to substances & effects

Substances alter excitability primarily by shifting the E/I balance. Depressants — alcohol, benzodiazepines, barbiturates — enhance GABA signalling or directly suppress excitatory tone. The result is sedation, slowed cognition, motor impairment, and at high doses suppression of protective reflexes.

Stimulants act in the opposite direction. Amphetamines and cocaine increase catecholamine activity, which broadly amplifies excitatory drive — producing the vigilance, quickened thinking, and heightened sensory sharpness that characterise stimulant effects.

Classic psychedelics produce a more complex pattern: they are thought to reduce activity in inhibitory interneurons, indirectly raising cortical excitability. This is believed to contribute to the amplified, sometimes overwhelming sensory and perceptual processing reported during a trip.

The rebound that follows sustained depressant use is one of the clearest demonstrations of the concept. The brain adapts to chronic suppression by upregulating excitatory systems; when the depressant is removed, that excess excitability is suddenly unchecked. The outcome can range from tremor and anxiety to seizures in severe cases — which is why abrupt discontinuation of alcohol or benzodiazepines is managed medically rather than stopped without supervision.