Benzodiazepines
Benzodiazepines Overview

Benzodiazepines are a class of prescription-only central nervous system (CNS) depressants used for the treatment of several conditions including anxiety disorder, seizure disorder, muscle spasms, insomnia and alcohol dependence. While benzodiazepines are invaluable for the treatment of these conditions, their potential for addiction and extensive side effect profile make them as dangerous as they are useful. Tolerance develops quickly and long term use of benzodiazepines can lead to both physical and psychological dependence. Once dependent, withdrawal from benzodiazepines can be deadly.

Benzodiazepines were initially introduced as a safer alternative to barbiturates, a dangerous class of drugs similar in effect to benzodiazepines. While safer than barbiturates and unlikely to cause significant harm when used appropriately, long term use of benzodiazepines must be approached carefully.

Listed below are examples of common prescription benzodiazepines.

  • Ativan (lorazepam)
  • Klonopin (clonazepam)
  • Librium (chlordiazepoxide)
  • Onfi (clobazam)
  • Valium (diazepam)
  • Xanax (alprazolam)

Benzodiazepines also go by street names such as benzos, downers, planks and tranks.

How Benzodiazepines Work in the Brain

Benzodiazepines work by enhancing the effect of a natural chemical in our brain called GABA (gamma-aminobutyric acid), the primary inhibitory neurotransmitter of our central nervous system. By increasing the activity of GABA, benzodiazepines “slow things down” in our brain, which is why they are effective at treating conditions such as anxiety and epilepsy. While this is beneficial for anxiety, slowing down brain activity too much can be dangerous, especially when benzodiazepines are combined with other drugs such as opioids or alcohol.

Medical Uses of Benzodiazepines
  • Insomnia – Insomnia is a sleep disorder characterized by difficulty falling asleep and/or staying asleep. Benzodiazepine’s hypnotic properties can induce a feeling of sleepiness, making it easier to fall asleep. While effective in the short term, long term use of benzodiazepines for insomnia may lead to dependence and withdrawal.
  • Generalized Anxiety Disorder (GAD) – Generalized Anxiety Disorder is an anxiety disorder characterized by persistent and unwarranted worrying.
  • Panic disorder – Panic disorder is a type of anxiety disorder characterized by episodes of severe, frightening anxiety accompanied by a spike in heart rate and blood pressure. Fast-acting benzodiazepines are effective for panic disorder as they act quickly to calm down an individual.
  • Seizures – Because benzodiazepines exhibit anti-convulsant effects, they are used to prevent and control seizures.
  • Agitation – In emergency cases of agitation, such as those resulting from drug-induced psychosis, the sedative effect of benzodiazepines can be helpful to tranquilize severely agitated individuals.
Benzodiazepine Side Effects

Benzodiazepines are associated with a plethora of physical and psychological side effects. The intensity of these side effects is directly related to the dose taken, with higher doses causing more pronounced effects.

  • Amnesia (impaired memory) – One of the most dangerous psychological side effects is amnesia, or the inability to remember events while under the influence of the drug. This had led to its use as a popular “date-rape” drug.
  • Drowsiness – Benzodiazepines can make a user feel tired and drowsy. It is important to not take benzodiazepines before driving or operating heavy machinery.
  • Depression – Long term use of benzodiazepines has been associated with depression.
  • Confusion – Users often feel confused while taking the drug and may take longer to make decisions.
  • Nervousness/Agitation – While generally effective at treating nervousness and agitation, some users may experience a paradoxical increase in feelings of nervousness and/or agitation.
Benzodiazepine Overdose

Benzodiazepine overdose occurs when an excessive dose of the drug is taken. Users who overdose on benzodiazepines may experience extreme sedation and/or confusion.

Acute overdose of benzodiazepines can cause respiratory depression, potentially leading to coma or death. While death due to benzodiazepine overdose alone is uncommon, the use of benzodiazepines in combination with other CNS depressants such as alcohol and opioids spells a recipe for disaster.

The graph above shows the number of overdose deaths due to benzodiazepines alone and in combination with other drugs such as opioids (dark green line). The data clearly shows that when benzodiazepines are combined with opioids, the probability for deadly overdose is significantly higher.

Benzodiazepine overdose can be treated with the drug flumazenil, which acts as an antidote to the sedative effects of benzodiazepines.

Benzos – The “Date Rape Drug”

There is growing concern regarding the use of benzodiazepines in drug-facilitated sexual assault, commonly known as “date rape.”  Benzodiazepine pills can be easily dissolved in beverages such as beer or glass of wine. Because they dissolve easily and may not change the color of the beverage, it can be difficult or impossible to detect. This is especially true for strong-tasting alcoholic drinks that mask the bitter taste of the pill. Once under the influence, the victim may fall asleep or become so disoriented they cannot defend themselves against an assault.

In one study that exampled urine samples of those suspected to be victims of drug-facilitated sexual assault, a staggering 15.4% of positive-urine samples contained benzodiazepines.

The drug Rohypnol (flunitrazepam), also known as “roofie,” is one of the most common benzodiazepines used in drug-facilitated sexual assaults. Despite not being available as a prescription drug in the United States, it is often imported illegally.

Benzodiazepine Addiction

Because benzodiazepines make users feel relaxed or even euphoric, their use is associated with a significant potential for abuse and addiction.

Signs of chronic benzodiazepine addiction may include the following:

  • Always appearing tired
  • Slurred speech
  • Unexplained feelings of depression or lack of motivation
  • Difficulty falling asleep if the user does not take the benzodiazepine
  • Exhibiting drug seeking behavior such as drug craving, deception, or stealing

While many users will abuse benzodiazepines obtained illegally, it is just as easy, if not easier, to abuse benzodiazepines with a valid prescription. In these situations, a user may take higher doses or take it more often than prescribed.

A 2018 study found that of the nearly one in eight Americans who had used a benzodiazepine within the following year, more than 17% had misused them, with misuse being defined as taking the drug in any way not consistent with how it was prescribed or having been obtained illegally. Misuse was found to be highest among adults aged 18-25 years old. Of those who had misused benzodiazepines, nearly half had explained that they used it “relax or relieve tension.” Among those taking benzodiazepines without a valid prescription, the most common source was a friend or relative.

Tolerance and Dependence

Tolerance

When benzodiazepines are taken for an extended period of time, the body develops tolerance to their effects, whereby a higher dose is necessary to achieve the same effect. Tolerance will develop quickly to the sleep-inducing properties of benzodiazepines, usually within days or weeks. Because of this, their use as a sleep aid should be limited only to a time necessary to treat insomnia. Tolerance also develops to a benzodiazepine’s ability to relieve anxiety. There is little evidence to suggest that they retain their anxiolytic effect after four months of continued use.

Dependence

In addition to the development of tolerance, psychological and physical dependence to benzodiazepines may occur if taken long term. Dependence occurs when the body requires the drug to function normally. Once dependent, if a user does not take the benzodiazepine, they will suffer withdrawal symptoms.

It is important to note that dependence to benzodiazepines can be both physical and/or psychological.

Psychological dependence occurs when the user must take the drug to feel normal, usually accompanied by drug-seeking behavior when the effects wear off.

Physical dependence occurs when the body experiences physical withdrawal symptoms when the effects of the drug wear off. Physical dependence can occur even if benzodiazepines are taken exactly as prescribed. Although physical dependence does not imply addiction, the two are often seen together.

Benzodiazepine Withdrawal

Because a user who is dependent on benzodiazepines requires the drug to function normally, they will suffer withdrawal soon after the effects wear off. Some of the symptoms associated with withdrawal include:

  • Sleep disturbance
  • Irritability
  • Anxiety and insomnia
  • Sweating
  • Muscle ache/pain
  • Drug craving
  • Seizures

The most dangerous withdrawal symptom associated with benzodiazepines is seizures, which can be life-threatening if not managed appropriately. How soon withdrawal symptoms will appear following the last dose depends on the half-life of the benzodiazepine.

The half-life of a drug is a measure of how long it stays in the body. Benzodiazepines with a short half-life are eliminated faster than those with a long half-life. Consequently, users who abuse benzodiazepines with a short half-life will suffer withdrawal symptoms sooner than those who abuse benzodiazepines with a long half-life.

Below is a table showing benzodiazepines with varying half-lives and the time until withdrawal symptoms will appear.

BenzodiazepineTime Until Withdrawal Onset Following Last Dose
Xanax (alprazolam)12 – 24 hours
Ativan (lorazepam)10 – 20 hours
Klonopin (clonazepam)1-3 days
Valium (diazepam)1-5 days
Treatment for Benzodiazepine Addiction

Treatment for benzodiazepine addiction involves slowly reducing the dose of the drug over time, a process known as tapering. The drug is tapered until it can be discontinued safely. How long a tapering period will last depends on many factors such as the length of abuse, dose of the benzodiazepine being abused and ability to tolerate dose reductions. An example tapering period may involve initially reducing the dose by 25%, then gradually decreasing by 5-25% every 1-4 weeks as tolerated.

It is incredibly important that benzodiazepines are not discontinued suddenly, also known as “cold turkey,” as this greatly increases the risk for life-threatening seizures.

Throughout the tapering period, a holistic approach is taken towards managing the user’s substance abuse habit. Because drug addiction is a psychological disorder, special care is taken to ensure the user’s mental health is maintained as well as their physical health. This can be accomplished by several means such as counseling and group therapy sessions

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