A variety of sedatives, hypnotics, and other central nervous system depressants have a reputation for causing memory loss, both clinically and among recreational users. Most common among these is alcohol/ethanol, which includes memory loss in its huge spectrum of deleterious effects, at least at higher dosages. Two main branches of prescription drugs also have this property: barbiturates such as Seconal and the now-generic (and mostly unprescribed due to abuse potential) phenobarbital, and benzodiazepines like Valium, Xanax, and the notorious amnesia-inducer Halcion.

Common to all of these is their activity in the brain's GABA (gamma-aminobutyric acid) system, specifically their ability to activate GABA-A receptors on certain neurons. Alcohol does this by directly mimicking the GABA molecule at GABA-A chloride channels, while barbiturates or benzodiazepines work by increasing either the duration or frequency, respectively, of channel opening. There is evidence that anandamide receptors, which are targeted by the cannabinoids in marijuana, also indirectly upmodulate GABA.

To understand what's going on here, one must first understand the function of the GABA system. While there are three kinds of GABA receptors, A, B, and C, the GABA-A receptors are of specific interest here as they are the common target of these drugs. In general these receptors are inhibitory, meaning that they regulate the excitability of their neurons -- more GABA activity means a greater stimulus is required to fire a given neuron. Some of the particular mood and behavior features regulated against by GABA-A are general anxiety, panic, fight-or-flight response, seizure threshold, and impulse control.

The counterpart to GABA's inhibitory pathway is the brain's primary excitory pathway, which uses glutamate as its neurotransmitter. One of the two kinds of glutamate receptor is called NMDA, which is (or at least seems to be) responsible for synaptic plasticity and long-term potentiation of neurons. NMDA channels, when exposed to glutamate and neuronal activity, pop open and let calcium ions in, strengthening future response to whatever stimulus caused the opening. Or in other words -- and all of this is covered in much greater depth in the NMDA node -- the channels allow for the functioning of long-term memory as it is currently understood.

Putting this all together, GABAergic memory disruption seems to occur because the lowered neuronal excitement levels cause a lowered possibility of NMDA channel opening. And since NMDA is the regulator of long-term memory, rendering it ineffective makes storage in LTM difficult or impossible. Since non-NMDA glutamate channels are less affected by overall neuronal excitement, often a large degree of brain function may remain, rather than unconsciousness or coma. Of course, all of this varies with dosage too, which is why a light alcohol buzz leaves no memory problems at all, where heavy binging can cause blackouts which last days.

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