Alprazolam (Xanax)

Patented in 1971 and approved for medical use in 1981, alprazolam is a prescription drug of the triazolobenzodiazepine class: a subtype of the larger benzodiazepine family characterized by the inclusion of a triazolo- ring structure.

Compared to other benzodiazepines, the unique characteristics of alprazolam are its fast-acting nature, short half-life, and increased potency.

Alprazolam is far more potent than diazepam, another leading benzodiazepine. Just 1 mg of alprazolam equals roughly 10 mg of diazepam [1].

Know colloquially as “bars,” alprazolam also enjoys a fair amount of renown in the designer drug community as a recreational drug.

IUPAC Name: 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Other Names: Xanax, Helex, Xanor, Trankimazin, Onax, Alprox, Misar, Restyl, Solanax, Tafil, Neurol, Frontin, Kalma, Ksalol, Farmapram, & Niravam.

Metabolism: Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and αhydroxyalprazolam.

Duration of Effects: Short-Acting (5-8 hours). The proper dosage of alprazolam lasts around 5 hours and has an elimination half-life of 11-12 hours.

How Does Alprazolam Work?

There are meaningful differences between them, but — in general — all benzodiazepines and their subsequent derivatives share the same basic mechanism of action, which gives rise to their anxiolytic, hypnotic, and muscle relaxant properties.

Benzodiazepines exert their effects by slowing down or “inhibiting” activity in the brain and central nervous system (CNS). There are a couple of ways they do this, but the most utilized pathway by far is through their interactions with gamma-aminobutyric acid neurotransmitters, otherwise known as GABA receptors.

GABA receptors are a class of neurotransmitters that cause an inhibitory response in the brain’s neurons.

Benzodiazepines work by potentiating this inhibitory function, usually by binding with the GABA-A transmitter subtype but at a site different from where GABA-A binds: this produces an allosteric effect — a fancy word which means there is increased activity in the receptor [2].

Upon binding, the GABA-A receptor opens its chloride channel, allowing negatively charged chloride ions into the neuron, thus affecting the neuron’s action potential and making it less likely to send electrical impulses throughout the brain and CNS. This inhibitory effect has been shown to reduce anxiety.

Alprazolam targets the GABA-A receptors to produce its effects. However, there are still many unanswered questions about how exactly benzodiazepines bind with GABA-A receptors and go on to produce their allosteric effect.

A lot of the confusion stems from the complex nature of GABA-A receptors. These receptors are made up of a total of 19 subunits. The classification and structure of the subunits is thought to have a determinative effect in the types of effects that are triggered. Essentially, benzodiazepines binding to different subunits trigger different effects [3].

When it comes to alprazolam, we do know that similarly to other classical benzodiazepines, it acts specifically through GABA-A receptors that contain α1/2/3/5, but not α4/6 subunit types. What is less understood, however, are the reasons for this specificity [4].

Is Alprazolam Safe? Risks & Side Effects

Alprazolam is classified by the United States government as a Schedule IV drug, indicating that although it does have accepted medical uses, it still carries the potential for misuse and tolerance, albeit at a lesser risk level than drugs classified as Schedule III.

Statistics show the increased rate of benzodiazepine involvement in overdose deaths is a significant cause for concern. A 2020 survey by the CDC showed that benzodiazepines were involved in 12.290 deaths in the US. Additionally, the NIDA published another study claiming that 16% of overdose deaths involving opioids also had the presence of benzodiazepines.

These trends are alarming but — more specifically — how does alprazolam factor into the larger context?

Studies show that alprazolam is not only the most commonly prescribed benzodiazepine in the United States but also the most common psychotropic medication in the US [1]. Compared to other benzodiazepines, alprazolam has a high potential for misuse.

Based on national emergency department (ED) visit data, alprazolam is the second most common prescription medication and the most common benzodiazepine to be involved in ED visits related to drug misuse (SAMHSA, 2013). This would mean that alprazolam is related to more ED visits than the next three commonly prescribed benzodiazepines (lorazepam, diazepam, and clonazepam).

CDC statistics further show their increased potential for danger and misuse. Between 2003 and 2009, alprazolam had the highest death rate increase of all benzodiazepines and the second highest overall at 234%, compared with 168% for benzodiazepines as a class (CDC, 2011) [1].

Less understood is why alprazolam is more dangerous than other benzodiazepines. It could be that the increased misuse statistics come more as a result of its increased usage relative to other benzodiazepines. Still, other factors like increased potency likely play a key role.