Benzodiazepines

Benzodiazepines are central nervous system depressants. They are among the most commonly prescribed in the U.S. today. There are over 15 types of benzodiazepine meds in the market, available to treat a wide range of physical and psychological maladies.

Benzodiazepines are anxiolytic (anti-anxiety), antispasmodic (muscle relaxant), anticonvulsant (prevents epileptic seizures) and sedative-hypnotic (sleep-inducing).

The most popularly prescribed benzodiazepines include Valium© (diazepam), Xanax© (alprazolam), Ativan© (lorazepam) and Librium© (chlordiazepoxide). Not legally prescribed but just as popularly known is the benzodiazepine Rohypnol© (flunitrazepam) for its reputation as a date-rape drug.

The human brain has a key neurotransmitter called gamma-amino butyric acid (GABA). This GABA inhibits motor neurons, so if there is GABA present, neuronal activity slows down or stops altogether. Benzodiazepines enhance GABA activity, effectively slowing nerve impulses throughout the body.

While dosage and absorption time varies among the different types of benzodiazepines, they all trigger the same physical effects. There are short-acting and long-acting benzodiazepines. A physician will choose either of the types (short-acting or long-acting) depending on what condition it is being prescribed for.

  

History

 Austrian chemist Dr. Leo Sternbach first discovered benzodiazepine in 1954 while working for Hoffman-La Roche. The drug was submitted for pharmacological evaluation where it was determined that it is superior to other related drugs. The first benzodiazepine was patented in 1959 (patent application 1958), and it was finally introduced into the market in 1960 as Librium (chlordiazepoxide).

Hoffman-La Roche continued pursuing molecular modifications and came out with Valium (diazepam) in 1963. Diazepam was shown to be 3x more powerful than chlordiazepoxide, with greater muscle relaxant properties. Hoffman-La Roche competitors also began looking for analogs.

In the early days, benzodiazepines appeared less likely to lead to dependence, particularly because compared to barbiturates, they did not cause respiratory depression. The medical community accepted benzodiazepines enthusiastically, resulting to its popularity and high demand from patients.

Other derivatives of the drug soon came out, including Mogadon (nitrazepam) in 1965, Dalmane (flurazepam) in 1973 and Xanax (alprazolam) in the 1980s. By the mid-1970s, over 8000 tons of benzodiazepine medications were being sold every year.3

It took a while for the realities of benzodiazepine to come to light, as researchers finally made the connection to GABA. By then glimpses of abuse and dependence have started to become evident. Soon, more guidelines (and legislation) were being published as to its use (and misuse). Of higher concern was the effect of benzodiazepines on elderly patients for their heightened sensitivity to its side effects.

 

Screening Cut-off and Detection Time for Benzodiazepine

 In drug testing, the cut-off level separates a negative and a positive test result. The cut-off levels are set at that point where drug detection happens with the smallest probability for false positives. It is imperative to note that a negative sample does not automatically mean that it does not contain any drug – it only indicates that it may contain a drug at such a low concentration that it is below the established cut-off.

 

 Specimen  Concentration Detection Time
Urine 300 ng/ml 3-7 days
Saliva 50 ng/ml Up to 48 hours
Hair 100 pg/mg Up to 90 days

 

Drug Type

Benzodiazepine is a depressant. Depressants slow down the activity of the central nervous system. These drugs are also called downers for the “relaxation” induce. Depressants relieve stress and anger, and often cause drowsiness or sleepiness. Depressants include the following:

  • Alcohol
  • Barbiturates
  • Benzodiazepines
  • Rohypnol (flunitrazepam)
  • GHB
  • Methaqualone
  • Tranquillizers

 

Forms and Routes of Administration 

Benzodiazepines come in the following forms and administered accordingly:

  • Oral – These drugs most commonly come in the form of tablets or capsules for oral administration.
  • Injection – They also come in liquid form (Valium, Ativan, Librium) to be injected either intramuscularly or intravenously. Versed© (midazolam) is made exclusively as IV.
  • Sublingual – Ativan comes in 0.5mg, 1mg and 2mg sublingual tablets to be dissolved under the tongue.

 

DEA Drug Class

Benzodiazepine is controlled under Schedule IV of the Controlled Substances Act. Schedule IV lists drugs, substances or chemicals that: 

  • have a low potential for abuse compared to Schedule III drugs;
  • have a currently accepted medical use in treatment in the U.S.;
  • may lead to limited psychological or physical dependence compared to Schedule III drugs.

 

Other Schedule IV drugs include:

  • Acetaminophen/Tramadol
  • Ativan (lorazepam)
  • Ionamin (phentermine)
  • Librium
  • Naloxone/Petazocine
  • Tramadol
  • Valium (diazepam)
  • Xanax (alprazolam)

 

Brand Names for Benzodiazepine 

 

Street Names for Benzodiazepines 

  • Benzos
  • BZDs
  • Candy
  • Dead Flower Powers
  • Goofballs
  • Heavenly Blues
  • Moggies
  • Qual
  • School Bus
  • Sleepers
  • Stupefy
  • Tranx
  • Valley Girl
  • Z Bars

 

Uses for Benzodiazepine 

  • Treatment of anxiety disorders
  • Management of convulsive disorders
  • Treatment of insomnia, night terrors and other sleep disorders
  • Treatment of mild or moderate depression and mood disorders
  • Treatment of involuntary movement disorders like restless leg syndrome, dystonia and dyskinesia
  • Treatment of symptoms of withdrawal from alcohol and other substances like delirium, anxiety, hyperpyrexia and seizures.

 

  • Recreational Uses for Benzodiazepine

 Non-medical use of benzos often begins when people feel worried or anxious and they want to be able to relax. They swipe a pill or two from a family member’s prescription left lying around in the house, thinking it would be harmless to use it just that one time. The next time they are stressed, they will simply take another pill, just to get through the moment of anxiety. Some people use them every other time they have difficulty sleeping until it becomes a habit. A more sinister non-medical use of benzos is for preying on unsuspecting victims, as is the case for Rohypnol (flunitrazepam), notoriously known for being a date-rape drug.

 

Short-term Effects of Benzodiazepine

Short-term side effects vary depending on the dose. At low to moderate doses, a user may experience the following side effects: 

  • Abdominal discomfort
  • Altered vision
  • Confusion
  • Constipation
  • Depression
  • Diarrhea
  • Drowsiness, lethargy, fatigue
  • Dry mouth
  • Impaired motor coordination
  • Impaired thinking and memory
  • Loss of appetite
  • Nausea/vomiting
  • Respiratory depression
  • Slurred speech, stuttering
  • Tremors
  • Vertigo

 

At much higher doses, extreme drowsiness occurs and on top of the low-dose side effects, users may also experience the following:

  • Euphoria
  • Hostile and erratic behavior
  • Mood swings
  • Slowed reflexes

 

Long-term Effects of Benzodiazepine

Each of the different kinds of benzo meds get eliminated from the body at varying rates. Some take a while so taking multiple doses over long periods can cause them to accumulate in the fatty tissues. This leads to a condition called over-sedation, the symptoms of which do not manifest right away, taking at least few days.

  • Confusion
  • Disorientation
  • Impaired thinking
  • Impaired memory
  • Impaired judgment
  • Muscle weakness, lack of coordination
  • Slurred speech

 

Benzodiazepine Dependence

Physiological and psychological dependence can result from benzodiazepine misuse depending on the drug’s potency, its dosage and the length of time it is taken. For example, alprazolam is highly potent and if taken at high doses, dependence can develop in as short as 2 months. With certain other benzos, tolerance occurs at around 6 months of use.

 Tolerance to the hypnotic effects of benzodiazepine appears to happen the soonest. It often occurs in as little as a few days of regular use. Tolerance to the drug’s anti-anxiety properties happens at a much slower pace, about a few months. As the effectiveness wears off, the user simply increases the dose just to get the same effect as before. It becomes harder for the user to stop using the drug once tolerance has set in because they start to experience withdrawal symptoms. This is called physiological or physical dependence.

 

Following is a list of benzodiazepine withdrawal symptoms:

  • Detachment from reality
  • Distorted perceptions/Altered sensations
  • Impaired sense of movement
  • Depersonalization
  • Visual and auditory hallucinations
  • Distorted body image
  • Tingling/numbness
  • Skin ‘crawling’
  • Hypersensitivity to light, sound, taste and smell
  • Muscle twitches/jerks
  • Tinnitus
  • Psychosis (occurs from abrupt withdrawal from high doses)
  • Confusion/delirium (occurs from abrupt withdrawal from high doses)
  • Convulsions (occurs from abrupt withdrawal from high doses)

 

Facts and Statistics 

  • Medical prescriptions are the primary source of benzo abusers. 
  • In 2010, the American Association of Poison Control Centers reported 81,427 cases, 31,255 of which are single exposures, and 11 fatalities were connected with benzodiazepine.
  • In 2010, an estimated 345,691 ER visits were attributed to benzodiazepines. 
  • A 2011 National Survey for Drug Use and Health (NSDUH) reported that an estimated 20.4 million people 12 years and older have misused benzodiazepines in their lifetime.
  • Benzodiazepine abuse is higher in men than in women (McCabe, 2005).
  • Benzodiazepine abuse is higher among alcoholics (Vorma et al., 2005).
  • The most common drugs used in combination with benzos are opiates like heroin. This is because the benzodiazepine reduces their cravings and/or withdrawal symptoms between highs.
  • Benzodiazepine is only shown as a primary drug of abuse in 12.9% of cases, but it is a secondary drug of abuse in 82.1% of cases.
  • Alprazolam (Xanax) is the most common benzodiazepine used for non-medical purposes.