Warning: long-term, regular use of these drugs, produces a dependence that can only safely be handled in the care of a hospital. Withdrawal can otherwise be fatal.

Also, its important to note that benzodiazepines are legitimate psychiatric medicines, with proven psychiatric, medicinal use. This page in no way advocates that one should act against the recommendations of their care providers.

Now,

Benzodiazepines (oftentimes called “benzos”) are minor tranquilizers. They are prescribed to treat…

This class of drugs works on an area of the GABA receptor, as does alcohol. It comes as no surprise then, that benzodiazepines are clinically used for several of the disorders that many people self-medicate with alcohol. Yet with alcohol, there is a much shorter duration, and it activates a variety of other non-GABA receptors that have no role in anxiety reduction. Benzodiazepines are specialized to work just on GABA receptors, effectively being better anxiolytics (anxiety-reducers) both in action and duration. That said, both have a similar withdrawal profile, and can be extremely physically and mentally addictive. The withdrawal makes them terribly difficult to stop using.

Each benzodiazpeine binds with varying strength to four regions on the GABA receptors. This explains their differnetial use. For instance, Xanax (alprazolam) is better for panic because it’s very selective for the α2 and α3 subunit. Restoril (temazepam) is used for insomnia, which correlates with its high activity on the α1 subunit.

 

Some of these images are quite detailed. No need to understand every notation.

 

Many subunits have been discovered

Image result for benzodiazepine subunit

 

Here we have a cryptic image detailing the brain  regions and effects that are affected via various binding sites on the GABA receptor.

 

Fig. (6). Side effect profile of benzodiazepines and neurosteroids based on the specific GABA A receptor selectivity and subunit abundance in the CNS. The schematic diagram indicates the respective GABA A receptor subunits and subunit compositions in the different brain regions responsible for Anxiety: cerebral cortex, amygdala (AM), bed nucleus of stria terminalis (BNST), hippocampus (HIP) [110, 111] Sedation: AM, formatio reticularis (FR) [112] Hypnosis: ventrobasal nucleus (VB), reticular nucleus (RTN), locus coeruleus (LC), Raphe nuclei (RN), substantia nigra (SN), ventrolateral preoptic nucleus (VLPO), tuberomamillary nucleus (TMN) [112] Abuse: N. accumbens (NA), ventral tegmental area (VTA) [113] Physical dependence: NA, VTA [114, 115] Tolerance: HIP, NA, AM [115] Withdrawal: HIP, NA, AM [115] Amnesia: cerebral cortex, HIP [112, 116] extra: extrasynaptical receptor syn: synaptical receptor IN: interneuron PN: pyramidal neuron GABA A receptor subunits or subunit compositions sensitive for the modulation by benzodiazepines are shown in red, those sensitive for neuroactive steroids are shown in blue. The diagram is not suitable to compare the absolute levels of various subunits in either brain region. The distribution of GABA receptor mRNA is not indicated. The interested reader is referred to [4, 117].  

As seen below, barbiturates, benzodiazepines, and alcohol bind to the GABA receptor. They produce similar effects.

 

Barbiturates were discovered before benzodiazepines, and from 1904 to the 1960’s, were prescribed frequently for anxiety, insomnia, epilepsy. These are reasons that people take benzodiazepines for today. The reason is that barbiturates are much more dangerous than benzodiazepines. They have a low therapeutic ratio. This means that the therapeutic dose and the lethal dose are close. In contrast, benzodiazepines have an extremely high therapeutic ratio. This is because they don’t increase GABA; they simply make what’s already there more efficient. They are positive allosteric modulators, whereas GABA is an agonist, and barbiturates become agonists at high doses.

 

Image result for benzodiazepine subunit

 

Much of the danger of benzodiazepines doesn’t come from brain damage if taken in obscene amounts. The danger comes down to two scenarios:

  1. Cold turkey withdrawal after daily use of a period of four weeks or longer.
    1. The withdrawal becomes life-threatening
    2. Brain damage can follow a too-fast withdrawal, regardless if one’s life is not in danger.
    3. Especially at first, one needs very close contact with one’s doctor, and a relatively close hospital.
  2. Combining depressants.
    1. Depressants mainly slow brain activity. Included are benzodiazepines, opioids, alcohol, and propofol.
    2. By itself, twenty times a daily dose of Klonopin abusive and dangerous, but not lethal. However, combining Klonopin with shots of vodka or percocet, can be. Never mix central nervous system (CNS) depressants. That’s how people die
    3. Notable fatalities include…
      1. Michael Jackson
      2. Jimi Hendrix
      3. Amy Winehouse
      4. John Belushi,
      5. Health Ledger
      6. Philip Seymour Hoffman
      7. Anna Nicole Smith

In a nutshell, benzodiazepines are horribly addictive and dependence-creating. Regular consumption of benzos for longer than a month tends to produce noticeable rebound effects when stopped, even if taken exactly by the instruction of a psychiatrist.

Withdrawal symptoms are essentially the same as alcohol, including, but not limited to…

  • Loss of appetite
  • Irritability
  • Insomnia
  • Vomiting
  • SweatingFatigue
  • Depression
  • Anxiety
  • Shakiness
  • Headache

Just the same as other drug addictions, here are some signs that one is addicted…

  • Spending less time doing previously important things, as a result of popping benzos
  • Using benzodiazepines for a longer period of time, than you had initially planned
  • The inability to stop abusing benzodiazepines, even though it’s caused personal, social, legal, or other significant problems
  • Your world revolving around use
  • The inability to stop or cut down use

People who want to get off of them after years of daily use (never abuse), will almost certainly find themselves in withdrawal at the intensity of hard drug cessation. The withdrawal syndrome of benzodiazepines may be the most torturous drug withdrawal known to man.

There are many websites that provide information, experiences, and advice for people who want to stop using. BenzoBuddies is one of the more prominent ones. Benzosupport is another one. One woman, Heather Ashton, dedicated a substantial portion of her life to studying benzodiazepines and withdrawal from them. She published a manual, free online, entitled Benzodiazepines: How They Work, and How to Withdraw (also known as The Ashton Manual).

Again, even if the patient is completely honest to their psychiatrist, and lets the doctor make the decisions, benzodiazepines can be as difficult to stop as hard drugs.

Below is a rough guess as to intensity of symptoms over time, after stopping regular benzodiazepine use. As can be seen, symptoms can persist even years after not having ingested a benzodiazepine. These symptoms are called Post-Acute Withdrawal Symptoms (PAWS). They occur for most people after daily use of an addictive drug over months or years comes to an end.

A bit more precisely, we see below that less than half of people felt recovered or almost recovered after nine months off of benzos. After 15 months (a solid year and a quarter, or, over 450 days without a benzodiazepine), a third of people still don’t feel almost recovered or recovered. This is solely to give a realistic estimate, not to push a benzodiazepine user one way or the other. Abuse, however, almost surely means withdrawal in the future.

Benzodiazepines have widely varying half-lives. A half-life is how long it takes for a drug to leave the body. We must also take into consideration any active metabolites, drugs that the main drug is broken down into in the body that has some psychoactive effect. There are pluses and minuses to stopping use of benzodiazepines with short and long half-lives. Stopping Xanax is extremely psinful, but for a short period of time. Stopping Klonopin is less harsh, but the withdrawal is a lot longer.

Unfortunately, there comes a point, when one has regularly used benzodiazepines long enough, that it’s only safe to withdraw from a long-acting benzodiazepine (such as Valium or Klonopin). This is because, at this point, dropping doses of short-acting benzodiazepines cannot be precise enough, and making an error and going down too fast could result in seizures and death. So, in this case, if one has been prescribed short-acting benzodiazepines (such as Ativan), they first switch to Valium or Klonopin before very, very gradually reducing how much they take.

Don’t know if you’re on a benzo? Just ask Google. Otherwise, drugs.com offers a fairly comprehensive list.

Common Benzodiazepines Available in the U.S.

Generic Name Brand Name Common Uses Half-life*
alprazolam Niravam, Xanax, Xanax XR anxiety, panic disorders half-life 6-26h (short-acting)
chlordiazepoxide Librax anxiety, alcohol withdrawal half-life 30-100h (long-acting)
clobazam Onfi Lennox-Gastaut syndrome, adjunct (seizures) half-life 71-82h (long-acting)
clonazepam Klonopin seizure disorder, panic disorder, neuralgia (nerve pain) half-life 20-50h (long-acting)
clorazepate Tranxene T-Tab anxiety, alcohol withdrawal, partial seizures half-life 20-100h (long-acting)
diazepam Valium anxiety, sedation, alcohol withdrawal, muscle spasm, seizure disorders half-life 20-100h (long-acting)
estazolam ProSom insomnia (short-term use) half-life 10-24h (medium-acting)
flurazepam Dalmane insomnia (short-term use) half-life 40-100h (long-acting)
lorazepam Ativan anxiety, insomnia (short-term use), seizures, sedation half-life 10-20h (medium-acting)
midazolam Versed sedation, preoperative; general anesthesia induction; seizures half-life 2.5h(short-acting)
oxazepam Serax anxiety, alcohol withdrawal half-life 5-15h (short-acting)
temazepam Restoril insomnia (short-term use) half-life 10-20h (medium-acting)
triazolam Halcion insomnia (short-term use) half-life 2-5h (short-acting)

Along with stimulants, benzodiazepines are the other class of psychiatric medication that are controlled substances, and thus can be particularly dangerous. Though they don’t provide as much of a high, they tend to provide a ridiculously hellish withdrawal that has a strong physical component. Some argue that stimulants aren’t physically addictive.

The depiction below lists benzodiazepines as, overall, more harmful than tobacco, amphetamine, and ecstasy

Sources: http://americanaddictioncenters.org, http://thebrain.mcgill.ca, Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424120/table/tbl1/, https://www.drugs.com/celebrity_deaths.html