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Benzodiazepines: Mother’s little helper

Benzodiazepines are one of the most well-known medications prescribed for an impressive variety of indications: muscle relaxation (spasms, dystonia), short-term anxiety such as panic attacks, alcohol withdrawal, acute violent episodes, as a hypnotic (for sleep), long-term anxiety as with generalized anxiety disorder, amnesic (pre-surgery), epilepsy, even to calm fears associated with visiting dentist.

Depressant medications have a rich history. Ages ago the most commonly used sedative was perhaps alcohol. One cringes at the thought of chugging whiskey to undergo limb amputations, but this was once reality. Opiates also boast a major role in the history of medicine. They still do, though their application has shifted drastically from sedative-related to pain management.

Thankfully, physicians and pharmacologists sought to move away from dangerous substances to those with fewer side effects (I’m looking at you addiction potential and respiratory depression). Barbiturates were soon ushered in and commonly used in the 1960s. Though, perhaps not soon enough, we reluctantly admitted they were hardly an improvement. During the early 1970s we also witnessed the rise and fall of Quaaludes as a common sedative/hypnotic. We’ve all heard stories, but the general theme is that Quaaludes are far more recreational than they are medicinal.

A worthy competitor would soon rise to pharmacological fame. The family of medications, benzodiazepines, had been identified years earlier in 1956 when Chemist Leo Sternbach reacted a basic benzodiazepine nucleus with methylamine in his lab at Roche Pharmaceuticals.


As can be seen in the images above, Sternbach’s research added methylamine to a benzodiazepine nucleus in position R2 above (The convention is that hydrogens are typically not labeled on large structures unless bound to a heteroatom, such as nitrogen). He found that his newly discovered white powder, named chlordiazepoxide, would make mice sleepy and calm. The drug was quickly marketed as Librium, and Roche worked to modify the molecule further in hopes of finding similar medications.

They soon discovered Valium (Diazepam) in 1963, which became the most prescribed drug in America between 1969 and 1982. Klonopin (Clonazepam) would also join the ranks of fellow benzodiazepines in 1975. The late 1970s would see benzodiazepines topping all lists of most frequently prescribed medications. The drugs were remarkable, and other pharmaceutical companies also began similar research. One of the most noteworthy benzodiazepines, Xanax (Alprazolam), was discovered in 1981 by Upjohn (now part of Pfizer).


A major aspect of the benzodiazepine’s improvement relative to previous generation’s medications was a lack of severe respiratory depression. Benzodiazepines became the most commonly prescribed drugs in the world. Some estimates suggest that 25% of all European women have taken them at least once a year. Benzodiazepines were even prescribed for “ordinary life stresses.” Acquiring a prescription was simple, as the indications were numerous.

Xanax Bars

Xanax Bars

Benzodiazepines remained in a positive light and were believed a safe and effective treatment until the 1980s.They were heralded as miracle cures less toxic and far removed from any addiction potential. Well, hindsight is a bitch that can be as ugly and the fierce withdrawals that were discovered to accompany benzodiazepine addiction.

In modern times, 29 benzodiazepines are available in both Europe and North America. Benzodiazepines are classified as Schedule IV in the United States Controlled Substances Act, identifying their clearly accepted medical use (though somewhat minimizing the high risk for abuse and dependence).

In the US, the most commonly prescribed benzodiazepines are Xanax (Alprazolam), Klonopin (Clonazepam), Ativan (Lorazepam), and Valium (Diazepam). Although physician preference may play a role in selecting the ideal treatment for an individual patient, several objective qualities guide the process. One important concept in this regard is a medication’s half-life. In medicine, a drug’s half-life is the average amount of time required for blood plasma drug concentrations to be halved. If a drug is cleared from the body quickly, then it has a very short half-life. Half-life durations and equivalent doses of some common US benzodiazepines can be seen in table 1 below. One should always keep in mind that these are averages, as a great deal of genetic variation exists among the population (giving rise to fields such as pharmacogenetics).

Half-life is mainly dependent on a couple of physiological factors. The first being our ability to metabolize and excrete a drug. An effective ability to enzymatically degrade a compound will decrease its half-life. A drug’s ability to bind blood plasma proteins (e.g. albumin) also can significantly impact its half-life. Drugs with a high affinity for plasma proteins have a tendency to remain in the body, increasing their half-life.

Selecting the right benzodiazepine for treatment is a delicate process. Perhaps the most important quality that dictates a patient’s treatment plan is their symptoms. For conditions that require daily anxiolytic treatment, such as generalized anxiety disorder, one would utilize a long-acting benzodiazepine like Valium (Diazepam). If a patient experiences acute panic attacks, such as those with post-traumatic stress disorder or panic disorder, one would utilize a short-acting benzodiazepine like Xanax (alprazolam).




The benzodiazepine family of medications has played a major role in medicine. From their hypnotic and amnesic applications to their anxiolytic qualities, benzodiazepines have made significant contributions to the field of medicine. Benzodiazpines have been around for decades and will not likely be removed from the physician’s arsenal any time soon.



“Mother needs something today to calm her down

And though she’s not really ill

There’s a little yellow pill”

-Mother’s Little Helper by The Rolling Stones


  1. Gotmilk has great benzos been buying from the for years. Gotmilk pharmacy

  2. Forget over priced pharma crap. Rc benzos have surpassed them long ago both in being more enjoyable, cheaper, stronger. And good luck finding the best pharma benzos (flunitrazepam, triazolam, midazolam, nimetazepam) in cheap powder form.

  3. Xavier Wellingtone III

    You guys are nuts to talk about benzos in such a casual way. I spoke with a woman with a ten-year plus Xanax addiction. She said her life spirals into total darkness and agony when deprived of the drug. Benzos gave psychiatry a free ride, without the serendipitous discovery of barbituates, psychiatry would have been relegated to the garbage dump it so richly deserves. Most modern psychiatrists are nothing but pill pushers.

  4. Uh, yes, they should be treated with respect, but how easily and how fast someone gets addicted is extremely variable. And the cases of mild/no wds are under reported in medical literature since if you feel fine after stopping you won’t go to your doctor and complain.

    I’m sorry for what she is going trough, but has she tried doing a slow diazepam taper? http://www.benzo.org.uk/manual/ This is the best collection of literature on the subject, it’s a bit outdated since it doesn’t include benzos unheard of before, nor other potential treatments (either alternatives or adjucts), ways of resetting tolerance back to baseline… tl;dr some of the info is outdated or not entirely correct, but what is important for your friend – first switch to a long acting benzo to minimize the fluctuations in blood levels and then slowly lower the dose. Even if you only reduce the dose of diazepam by 0.25mg per week it’s a success. It might take years but she can get off them quite easily. It’s not strictly necessary to use diazepam, but I’d advise against nitrobenzos or fluorobenzos or triazolo benzos since they are too enjoyable.

  5. Thanks for the article Kevin, looking forward to more!
    It would be EXCELLENT to see an article on RCs, particularly 1P-LSD and the NBOMe compounds. 1P-LSD has strange properties and seems to be as serotonin receptor agonist. Seems to be an LSD prodrug? Any in-depth commentary would be much appreciated. The whole class of psychedelic RC’s is a brave new world that desperately needs to be elucidated for the health and well-being of thousands of new users. Thanks.

  6. i wish i was never put on xanax in the first place…the withdrawals last years and are the worst thing ive ever experienced…and ive had my share of drug withdrawals…
    benzos are evil

  7. Anyone have a good current supplier?

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