Not all benzodiazepines are created equal
In the absence of dependency and addiction, benzodiazepines are life-saving medications. But once a dependency has formed, which can be no fault of your own, you may find yourself in a support group as you embark on the journey of tapering off or learning more about the withdrawal syndrome. You may have heard in BWS support groups that some benzodiazepines earn themselves raunchy nick-names like “Xanthrax,” and on the surface, this is for somewhat obvious reasons – they can really make you feel like you’re being poisoned when you’re adversely affected by them. But did you know that clonazepam (Klonopin, Rivotril) is known as “Napalm” to some scientists, and that it’s only prescribed for epileptic disorders in some countries? And have you ever heard that “a benzo is a benzo?”
Well, we know that it’s true that all benzodiazepines are benzodiazepines, in a similar way that all antibiotics are antibiotics – but they don’t all work the same way. This is one reason why the late Dr. Reg Peart theorized that diazepam substitution tapering requires a crossover adjustment period. Every benzodiazepine has a higher or lower binding affinity for the various functions of the GABAA receptor (GABAAR), the receptor site that benzodiazepines, z-drugs and barbiturates bind to.
The functions of GABAA include:
- anxiolysis (anxiety relief)
- hypnosis (sleep-inducing)
- myorelaxation (muscle relaxation)
- anticonvulsive (anticonvulsant)
- amnesia (memory loss)
With that in mind, it’s well-known to those of us who’ve studied this subject matter that clonazepam’s binding affinity for the anticonvulsant function of GABAAR is especially high. It binds very tightly to GABAAR . It binds tightly to any area that it binds to. This tight binding affinity, along with the fact that clonazepam is a nitrobenzodiazepine, is why it’s sometimes been referred to as “Napalm.” Although it’s not the only nitrobenzodiazepine – there are others such as nitrazepam (Mogadon – why didn’t they just brand it as “Nitro?!”), flunitrazepam (Rohypnol), nitrazepate (Lorzem), among others. Of these, clonazepam is more popular. And it’s very strong.
Because of all this, it’s not commonly prescribed in countries for anything other than epileptic disorders other than the US for the most part. One reason why it’s prescribed to anxiety disorder and even manic patients in the US, however, is because it has a longer half-life and duration of action of therapeutic effect; these are two desirable traits when shorter half-life BZDs fall short because the short half-life BZs necessitate more frequent dosing. There’s not quite as much up and down in blood concentration with longer half-life BZs, and these include but are not limited to clonazepam (Klonopin), diazepam (Valium) and chlordiazepdoxide (Librium). And as such, short-acting BZDs such as alprazolam (Xanax), lorazepam (Ativan) and oxazepam (Serax) would conversely result in a higher incidence of interdose withdrawal symptoms. Since some people don’t seem to metabolize or tolerate diazepam very well, sometimes they taper using clonazepam or whatever original benzo they became dependent on. It’s certainly not impossible to taper directly off of clonazepam or other potent BZDs if you can find a way to make small enough reductions to them – their lowest strength scored (evenly distributed) tablet formulations are typically no lower than a potent 0.5mg.
So why is Xanax more addictive, and why is it sometimes called “Xanthrax” by those who’ve been bitten by it? Fortunately, it has nothing at all to do with anthrax.
ohhh kay. phew!
First, a recap on the importance of distinguishing addiction vs. dependence: they’re not the same thing, and most people who suffer from benzodiazepine withdrawal syndrome aren’t addicts. That’s right, many people stuck on alprazolam (Xanax) aren’t abusing it. But it’s arguably more addictive than other BZDs, with dependency forming rapidly in some individuals. Alprazolam (Xanax) earned its reputation of being the most dangerous and toxic benzodiazepine for its notorious high potency and short half-life. That is, a tendency to hit you hard and leave you fast – setting anyone who’s dependent on it up for severe interdose withdrawal, and as a result of that, possibly a tougher time tapering off of it along with increasing dosages, which might look like addiction. Of more particular interest, alprazolam was first marketed to people with both anxiety and depression because it hits on the 5-HT serotonin receptor, beta adrenergic receptors, and possibly other neurotransmitters in a stimulating way. It differs significantly from other BZs, especially diazepam, in this way, although many other BZs can and do affect 5-HT and other receptors either directly or indirectly. But alprazolam was really pushed for this as the effects were more prominent.
The extra molecular ring makes alprazolam one among the triazolobenzodiazepines; these are benzodiazepines that differ from classic benzodiazepines and the nitrobenzodiazepines. Most traditional benzodiazepines have three rings in their molecular structure, triazolobenzodiazepines have four. More classical BZs end in the suffix “-pam,” while triazolobenzodiazepines end in “-lam.” It’s all a nice, technical-sounding way of describing a toxic roller-coaster hell ride in pill form, if you end up dependent on it, that is. A pill that’s both a stimulant and a tranquilizer – an upper and a downer – at the same time. Perhaps this could explain why alprazolam is more popular in people who actually abuse benzos.
The science behind the way many of the more common BZDs work makes it easier to understand why benzodiazepine withdrawal syndrome experts such as Professors Ashton and Lader developed diazepam substitution tapering as the most effective tapering protocols to discontinue benzodiazepines altogether. If all benzodiazepines were the same, we wouldn’t need diazepam substitution tapering (see: Ashton Protocol). Although some people may experience depression as a side effect of diazepam, its long half-life and tendency to leave the body more gently still makes diazepam the most ideal benzodiazepine to taper from, according to Ashton.
UpJohn, the makers of Xanax, made another once-wildly-popular triazolobenzodiazepine that had similar pharmacological properties as Xanax: Halcion (triazolam). Ironically, however, the British government actually banned Halcion years ago. Its side effects, which are very similar to those reported by those adversely affected by Xanax, seemed to be more intense than the already bad side effects observed in some people on classic benzodiazepines. The way that triazolobenzodiazepines appear to cause both sedation and stimulation of the CNS may be why Xanax (alprazolam) was marketed for both anxiety and depression, but as we know now, the theory for why was very flawed. It has been reported far too often that the volatile side effects of Xanax seem to be one of the many reasons why it’s often painted as “the worst benzo,” with the U.S. state of Alabama possibly upscheduling it to Schedule II as it seems to be more addictive.
Vintage ads marketing Xanax for clinical anxiety associated with depression:
–> Gallery of more vintage pharmaceutical ads for tranquilizers <–
Beware. Some of them are really creepy now that we know what we know.
Just how do pharmaceutical companies get away with marketing a benzodiazepine for both clinical anxiety and depression? That extra ring in their molecular structure – the triazolo ring – makes them different. Alprazolam’s sedative effects are exerted along with… hyperexcitability on the CNS. What a mess. Many people who have paradoxical reactions report to have had these to alprazolam and other triazolobenzodiazepines, such as midazolam (Versed) which is often used before and during surgeries for sedation and amnesia. Midazolam acts briefly, but powerfully, on GABAAR’s hypnotic (sleep-inducing) functions.
But none of this is the most “explosive” news about the problem with the pharmacological properties of these medications – what’s truly devastating to most people who know this stuff, is that sometimes, their doctors and even their pharmacists, don’t.