On Xanax
As some of you know, I had a dark period in my life caused by an acute dissociative episode. Since then, I learned quite a lot about mental health, depression, antidepressants, and other psychiatric medications.
The first real problem I had was chronic, untreated anxiety that spiraled into an episode of depersonalization and derealization after a night of heavy alcohol consumption. The second real problem was that I tried to self-medicate with Xanax, a fast-acting, anti-anxiety medication, known for its potent effect and a high risk of developing tolerance and addiction.
Xanax or Alprazolam belongs to a group of medications called benzodiazepines. These medications are one of the most-prescribed types of medications in the world, and their numbers are rising year by year in the US.
How do benzodiazepines work?
Imagine a nerve cell. Your nerve cells, also called neurons, work by transmitting a signal along their long bridges called axons. In order for the signal to be transmitted, there needs to be a surplus of positive electric charge inside them. These positive charges arise from positive ions like sodium and potassium that are transmitted through various channels on the membrane of said neurons. There are also negative ions that make the nerve cells “less positive” and, because of that, less likely to transmit a signal. Negative ions such as chloride ions enter the nerve cell through their channels, like the chloride channel, for example. Some channels are opened by nerve potential, but others by various neurotransmitters such as acetylcholine or GABA, for example.
Benzodiazepines work by binding to GABA receptors, a type of receptor that acts as an opener of the chloride ion channel, thus allowing the excess chloride ions to enter the nerve cells, inhibiting the transmission of nerve signals.
Since nerves in some part of your brain become “less active”, you suddenly feel the relaxation coming over you, and you start to enjoy a break from your anxiety.
The tolerance
The problem with benzodiazepines isn't their neurotoxic or damaging effect on your brain, but rather the much more subtle buildup of tolerance over time.
We thought that the buildup of benzodiazepine tolerance includes the loss of all of their effect over time. New studies suggest otherwise.
I knew many people who took anti-anxiety medication and seemingly never developed tolerance to them, which is contrary to the popular belief that they lose their effectiveness even after two weeks of everyday use.
I always wondered how some people seemingly never developed tolerance to these medications, even though my psychiatry professors, doctors, and pharmacists said that tolerance begins after 2 to 4 weeks of everyday use. We thought that tolerance was a sort of loss of all the effects of medication after some time, and now we know that tolerance can build up for different effects and even side effects.
Benzodiazepines like Xanax have many effects, like a sedative effect (makes you tired), a hypnotic effect (makes you fall asleep), an anticonvulsant effect (stops a convulsive episode), an anxiolytic effect (gets rid of your anxiety), and an amnesic effect (makes you forget).
Studies show that after 2-3 weeks, people develop a tolerance for all of the effects except the anxiolytic and amnesic effects. Does this mean that no matter how long you take Xanax or other medication from this group, it will always calm down your anxiety and, in higher doses, make you forget certain events?
Absolutely not.
While the tolerance to anticonvulsant and sedative effects takes about 2 to 3 weeks, the tolerance to anxiolytic effects takes a bit longer. How much longer, you might ask? Well, it depends on several factors.
Type of benzodiazepine
Short-acting drugs (like Xanax) tend to lead to faster tolerance than longer-acting ones (like clonazepam). Short-acting benzodiazepines provide rapid relief that strongly reinforces use by creating a quick reward loop in the brain, and because they wear off quickly, they can trigger mini-withdrawal symptoms like rebound anxiety or irritability between doses, further driving repeated use and accelerating dependence.
Age and liver function
Slower metabolism from aging or liver impairment may delay tolerance, but also increases the risk of drug accumulation and side effects. The key is that tolerance isn’t just about how fast the brain adapts, it’s also about how much and how often the brain is exposed to the drug, which is greatly affected by metabolism.
On top of that, medication dosage and individual differences like genetics and metabolism all play a role.
But how exactly does tolerance form? Let’s look into our neurons.
As I previously said, benzodiazepines work primarily on GABA receptors, which act as a switch that lets negative ions enter our neurons, making them less likely to transmit signals from one neuron to another. If benzodiazepines are used for a long period, our neurons reduce the number of GABA receptors or make them less sensitive to maintain balance ( in a process called downregulation).
Since there are fewer receptors, there is less space for medication to bind to.
If you take benzodiazepines for even longer, you might even change your brain structure. For instance, the number of synaptic connections (which help transmit signals) between neurons can change, contributing to a reduced neural responsiveness to the drug.
In other words, there may be a place for medication to bind to, but the neuron itself can’t transmit the signal to other neurons, making the medication less effective.
Xanax and other benzodiazepines are great medications when used wisely. They can greatly improve symptoms of someone’s anxiety when used correctly, but can also have devastating consequences when misused. People who are prescribed antidepressants are also prescribed benzodiazepines, since the immediate effect of some antidepressants is increased energy without lowering the depressive symptoms. This means that at the start of the therapy, depressed people get a sudden burst of energy, which prompts them to commit suicide.
This effect is greatly reduced when people take anti-anxiety medications, effectively making benzodiazepines lifesavers in this case.
On the other hand, I had the misfortune of seeing some of the patients during the withdrawal period from benzodiazepines, and I can tell you that it’s in the top 10 worst things I've seen in medicine. And I’ve seen a lot of things.
If anyone you know suffers from anxiety or any other mental health condition, please urge them to talk to a professional. Unlike fractured bones or diabetes, there is still a huge stigma in our society concerning mental health.
If you ever find yourself in a similar situation, talking to anyone can have a huge impact on your well-being. No matter how hard it gets, there are always people who have gone through the same thing, and there are people who will help you. You are not alone. Find the strength to ask for help.
Summary:
Benzodiazepines work by enhancing the calming neurotransmitter GABA, allowing chloride ions to enter nerve cells and quiet overactive brain activity. This produces rapid relief from anxiety, sedation, sleep, and muscle relaxation. The problem lies not in brain damage, but in the gradual buildup of tolerance and dependence. Tolerance develops at different rates; sedative, hypnotic, and anticonvulsant effects fade after just a few weeks, while the anti-anxiety effect persists longer but still weakens with ongoing use, especially with fast-acting drugs like Xanax that reinforce a cycle of relief and withdrawal. Age, liver function, genetics, and dosage all influence how quickly tolerance develops. Over time, the brain adapts through downregulation of GABA receptors and changes in synaptic connections, making the medication less effective and withdrawal extremely challenging. Despite these risks, benzodiazepines can be essential in psychiatry, particularly at the beginning of antidepressant therapy, when increased energy without relief of depressive thoughts can raise the risk of suicide. Used wisely, they can be lifesaving. The key lesson is that mental health struggles should never be faced alone; professional help, guidance, and support are crucial.