Benzodiazepines

Also known as

Benzos, jellies (temazepam), valium (diazepam), rohypnol, roofies (Flunitrazepam), blues, blueys, tranx, roche's, mother's little helpers, duck eggs (temazepam), V's, sleepers, downers, pills, xannies, serras (Serepax®), moggies (Mogadon®), normies (Normison®)

Classification

Anxiolytic, sedative, depressant, anticonvulsant

Overview

Benzodiazepines (or 'benzos') are a group of synthetic chemicals that act as depressants on the central nervous system. They act as, and are sub divided into, anxiolytics, hypnotics, sedatives and anti-convulsants. They also work as muscle-relaxants. Many different benzos exist, the most commonly prescribed ones being Diazepam (Valium), Alprazolam (Xanax), Lorezepam and Temazepam. Other benzodiazepines also include Oxazepam, Midazolam and Etizolam .

There are more than 35 benzodiazepines under international control, that being the 'United Nations Convention on Psychotropic Substances' .

Benzodiazepines are depressant drugs. This means that they slow down the activity of the CNS and the messages travelling between the brain and the body. They do not necessarily make a person feel depressed. Other depressants include alcohol, cannabis and heroin.

Benzodiazepines, also known as minor tranquillisers, are most commonly prescribed by doctors to relieve stress and anxiety and to help people sleep. However, there is increasing concern among medical professionals about the risks of using these drugs, particularly when they are used for a long time.

Some people use benzodiazepines illegally to become intoxicated or to help with the 'come down' effects of stimulants such as amphetamines or cocaine .

Benzodiazepines have been available since the 1960's and have since been used to treat problems such as severe anxiety and insomnia. Before benzodiazepines, such conditions were treated with barbiturates, which were commonly linked to fatal overdoses. They are sometimes referred to as 'benzos' or BZD/BDZ. They should not be confused with the more recently introduced drugs BZP and 'benzo fury'.

There are a wide variety of benzodiazepines, which differ in the balance of effects they have, and how long they last. The most well-known types include diazepam (Valium), temazepam, nitrazepam and others, usually with names ending in -pam or -lam. Flunitrazepam (Rohypnol) is a benzodiazepine but due to suggestions that it has been used as a 'date rape drug', it is now illegal in some European countries, outside of medical use .

What does it look like?

Tablets, capsules, injectables (e.g. diazepam, lorazepam, midazolam), suppositories .

The appearance of each drug varies widely. Most are distributed as tablets or capsules. A small number of unregulated compounds are sold as powders. A few also come in preparations for injection, such as Valium ampoules, which command a higher street value.

Different brands of drug will vary from company to company. Tablets will vary in colour, shape and markings.

The mainstay of the street benzodiazepine market has, for a number of years, been diazepam. The most widespread and popular strength, a 10mg tablet, is often a scored blue tablet. As a result, people manufacturing tablets to sell as diazepam invariably produce a blue tablet. These can vary massively in consistency and strength. Some are merely white powders, dyed blue and compressed in to tablets .

While benzos usually come in tablet or capsule form, there are various brands, sizes, shapes and colours .

Source

Benzodiazepines are widely prescribed as sedatives, to combat anxiety, as skeletal muscle relaxants, anti-epileptics and anti-convulsants. However, some benzodiazepines leak onto the street, and are quite widely misused.

Benzodiazepines, especially diazepam, have been illicitly imported in to the UK. Some have been entering from Eastern Europe and sold on the illicit markets. Others have been ordered on line from one of the many Internet Pharmacies. Some of these tablets are fake, or of variable quality.

Since around 2009, we have also seen the rediscovery of abandoned experimental benzodiazepines or the emergence of new ones that are not currently restricted. This has resulted in unregulated sale on-line and in 'head-shops' of benzodiazepines. Some of these have since been regulated but there are several that, at the time of writing, are still sold in the UK.

The imported and regulated drugs mean that benzodiazepines remain widely used and available, even though the number of prescribed drugs has decreased in recent years.

Since around 2008, there has been a significant increase in the supply of benzo-type drugs on websites supplying other Novel Psychoactive Compounds. The first compound supplied, Phenazepam, has since been made a Controlled Drug. However a number of other compounds have since emerged. These include Etizolam, Deschloroetizolam, Flubromazepam and a number of others .

Diverted from manufacturers, pharmacies and GPs prescriptions .

Prevalence

The INCB statistics for 2009 show that Europe has the highest average consumption of both for sedative-hypnotics and for anxiolytics, expressed as defined daily doses for statistical purposes (S-DDD) per 1,000 inhabitants per day.

In the case of anxiolytics, the figure for European consumption was around 37 S-DDD in 2001 - 03. which rose to around 46 S-DDD in 2005 - 06, and then dropped to around 42 S-DDD in 2007 - 09.

For sedatives it was approximately 24 S-DDD in 2005 - 07 up which fell to 22 S-DDD in 2006 - 08.

In 2007, global consumption of anxiolytics was around 22 billion S-DDD, which first rose to around 25 billion S-DDD and then dropped to around 21 billion S-DDD in 2009.

There is a lack of self-reported prevalence data on the use of benzodiazepines in the general population. Monitoring is limited by the very broad range of benzodiazepine products available in Europe and the lack of clear definitions for the general population to report their levels of use.

Among 15- to 16-year-old school students, lifetime prevalence of the use of 'tranquillisers or sedatives without a doctor's prescription ranged from 2% to 15% in the 24 EU Member States and Norway with ESPAD surveys in 2011, with six countries reporting prevalence levels of 10% or more , .

Prescribing trends

According to the MHRA (Medicines and Healthcare Regulatory Agency) [prescribing of benzodiazepines in England] has been relatively constant between April 2008 and April 2012, ranging between 10.9 and 11.1 million prescriptions annually.

The prescribing of benzodiazepine hypnotics (flurazepam, loprazolam, lormetazepam, nitrazepam, and temazepam) has declined from 2008 to 2012, while that of benzodiazepine anxiolytics (alprazolam, chlordiazepoxide, lorazepam, and oxazepam) has increased slightly, but prescribing has increased most for benzodiazepines that can be used for other purposes (clobazam, clonazepam, diazepam, and midazolam) .

Prevalence of recreational use

According to a study from November 2014 published in the British Journal of Psychiatry, of 1500 respondents 7.7% (n = 116) had misused one or more benzodiazepines. Almost 15% of those misusing at least one of these drugs did so once weekly or more often. The main reasons reported for their use were to help sleep (66.4%), to cope with stress (37.1%) and/or to get high (31.0%). A total of 31% obtained the medications from multiple sources; healthcare professionals (55.2%) and friends/family (39.7%) most commonly.

There is no known illicit manufacture of benzodiazepines. The benzodiazepines which circulate on the illicit market are diverted from legitimate clients either by over-prescription, that is to say individuals selling on part, or all, of their legitimately prescribed drugs, or by theft from pharmacies, hospitals or retailers .

Street price

At a street level, benzodiazepines have a very low value, typically around 50p per tablet. Ampoules can cost a pound or two .

Why take it?

Sought after effects

• calm and relaxed,
• induces long periods of sleep ,
• relaxation,
• reduced anxiety,
• euphoria .

Undesired effects

• short-term memory loss,
• reduced mental alertness,
• anxiety ,
• drowsiness,
• light-headedness,
• loss of coordination,
• confusion .

Pharmacology

Benzodiazepines affect a key neurotransmitter in the brain called GABA. This neurotransmitter has an inhibitory effect on motor neurons, thus the presence of GABA slows or stops neuronal activity. Benzodiazepines enhance the activity of GABA, effectively slowing nerve impulses throughout the body. The human nervous system has two different types of benzodiazepine receptors: one that causes the anti-anxiety effect, and one that elicits the sedative effect .

Although most benzodiazepines trigger the same physical effects, their dosage and absorption time into the bloodstream can vary widely . The medications are broken into two separate categories for classification - short-acting and long-acting . A short-acting benzodiazepine is cleared from the body in a short period of time, whereas long-acting benzodiazepines may either accumulate in the bloodstream or take a much longer period of time to leave the body. A particular benzodiazepine's classification determines what it is prescribed for, as well as its potential for tolerance, dependence, and abuse .

Benzodiazepines elicit five principle pharmacological effects - namely: anxiolytic (anxiety-reducing); sedative; hypnotic (sleep-inducing); muscle relaxant and anticonvulsant. They may be prescribed to mediate one or more of these effects. They are also used during alcohol detoxification and to reduce hyperexcitability and/or aggression during acute psychotic episodes. Additionally at high doses, some benzodiazepines also have amnesic effects which are useful for surgical procedures.

These effects (and associated adverse effects) arise from the action of benzodiazepines on the main inhibitory neurotransmitter GABA.

GABA is a chemical that occurs naturally in the body and transmits inhibitory signals from nerve cells (neurons) throughout the CNS, to target cells that exert its actions. These signals are transmitted across small gaps between nerve and target cells called synapses. It causes a reduction in the excitability of neurons and is also responsible for the regulation of muscle tone in humans.

Both benzodiazepines and GABA bind to postsynaptic GABAA receptors causing a decrease in the activity of nerve cells that regulate movement (motor neurons).

Benzodiazepines bind to the gamma subunit of GABAA receptors which increases the opening of the chloride channels. Increased movement of chloride ions through these channels increases the postsynaptic membrane's resistance to excitation.

Benzodiazepines share a common basic chemical structure and the addition of different chemical groups to this structure gives rise to their specific properties.

The affinity of each benzodiazepine to water affects how quickly they begin to act after being taken and how long they continue to act for. Less water soluble benzodiazepines (such as diazepam and midazolam) begin to act more quickly than those that are more water soluble (such as lorazepam and alprazolam) but also tend to be shorter-acting .

Benzodiazepines are a group of CNS depressants which induce feelings of calm (anxiolysis), drowsiness and sleep. They act by facilitating the binding of the inhibitory neurotransmitter GABA at various GABA receptors throughout the CNS. Because they have a lower tendency to cause a potentially fatal CNS depression compared to earlier drugs such as barbiturates, benzodiazepines are widely used in medicine for the treatment of anxiety (anxiolytics) and insomnia (sedative/hypnotics), as well as other psychological conditions such as panic attacks and panic disorders. There is no clear division between anxiolytics and hypnotics, since most anxiolytics will induce sleep if taken at night and most hypnotics will sedate when taken during the day.

Different benzodiazepines vary in the rate in which they are metabolised to pharmacologically active forms and particularly in their half-lives: short-acting drugs have a half-life of less than 24 hours e.g. midazolam; intermediate-acting compounds such as nitrazepam have half-lives greater than 24 hours, whereas long-acting compounds such as diazepam have half-lives greater than 48 hours. Such half-lives vary between individuals, and the elderly tend to eliminate these drugs much more slowly. They are thus more at risk from the side-effects which include drowsiness, ataxia (staggering gait), mental confusion, impaired judgement and anterograde amnesia. There is a significantly increased risk of adverse events in the elderly such as falls, diminished cognitive function and driving impairment, although the latter is not confined to the elderly. The European prevalence studies show that, excluding alcohol, benzodiazepines are along with cannabis the psychoactive substances most prevalent in the driving population. Experimental studies show that these drugs impair driving ability and when alcohol is also used, the risk of being involved in or responsible for a road accident is significantly increased.

Benzodiazepine intoxication can be associated with behavioural disinhibition, potentially resulting in hostile or aggressive behaviour. The effect is perhaps most common when benzodiazepines are taken in combination with alcohol. The combined use of alcohol and benzodiazepines also increases the risk of a fatal overdose because both act as CNS depressants. A similar fatal interaction can occur when opiates are taken with benzodiazepines as part of a pattern of \gls{polydrug use}. A significant number of problem drug users swallow, 'snort' or inject high doses of benzodiazepines to enhance the euphoriant effects of opiates or to minimise unpleasant effects of psychostimulants. The EMCDDA's Annual report on the state of the drugs problem in Europe highlights the fact that concomitant use of benzodiazepines and opiates is a major risk factor in drug-related deaths. Apart from the increased risk of fatal overdoses, the usual injection-specific diseases such as tissue damage, gangrene and transmission of HIV and Hepatitis C also occur if the drugs are injected.

There is also the risk of cross-dependence developing to benzodiazepines. Medically, benzodiazepines should only be used for the short-term relief of anxiety or insomnia which is severe and disabling. This is because tolerance and dependence can occur just weeks after use has commenced. Withdrawal signs and symptoms can be classified as major or minor, like those of the alcohol syndrome. According to that classification, minor symptoms include anxiety, insomnia and nightmares. Major symptoms include perceptual disturbances, psychosis, hyperpyrexia and life-threatening convulsions .

The human brain contains many different neurotransmitters which are responsible for sending messages between brain cells, these messages can have either 'tranquillizing' or 'excitatory' effects.

When someone feels overly anxious, the brain becomes 'excited' and over-active, tranquillizing transmitters need to quickly send messages to brain cells to slow down activity in the brain and reduce the symptoms of anxiety.

GABA is the brain's tranquilizing neurotransmitter, and billions of brain cells respond to its signals.

Benzodiazepines work by enhancing the effect of the neurotransmitter GABA. The drugs contain chemicals which add to the calming effect already produced by the human body and essentially keep the brain in a more 'tranquillized' state .

Benzodiazepines affect a key neurotransmitter in the brain called GABA. This neurotransmitter has an inhibitory effect on motor neurons, thus the presence of \gls{GABA} slows or stops neuronal activity. Benzodiazepines enhance the activity of GABA, effectively slowing nerve impulses throughout the body. The human nervous system has two different types of benzodiazepine receptors: one that causes the anti-anxiety effect, and one that elicits the sedative effect .

Although most benzodiazepines trigger the same physical effects, their dosage and absorption time into the bloodstream can vary widely . The medications are broken into two separate categories for classification-short-acting and long-acting. A short-acting benzodiazepine is cleared from the body in a short period of time, whereas long-acting benzodiazepines may either accumulate in the bloodstream or take a much longer period of time to leave the body. A particular benzodiazepine's classification determines what it is prescribed for, as well as its potential for tolerance, dependence, and abuse .

Mode of use

Benzodiazepines are usually swallowed as tablets but can be injected for both medical and non-medical purposes and there are some reports of intranasal (snorting) misuse .

Methods of use vary greatly depending on the purpose of the administered benzodiazepine. The most common method of ingestion is orally, in tablet or capsule form. Valium©, Ativan©, and Librium© are also sometimes dispensed intravenously, while midazolam (Versed©) is used exclusively as an intravenous medication. Ativan© comes in a tablet form that can be dissolved under the tongue .

Benzodiazepines are usually swallowed. Some people also inject them .

Signs of usage

Aside from physical evidence such as packaging, there are few markers for benzo use. Illicit fake diazepam can cause blue staining to lips and tongue. Otherwise indicators are simply drowsiness, relaxation and possibly appearing drunk, but without the smell of alcohol.

Whilst older benzos will show up on urine tests, some of the newer products such as Etizolam are sufficiently structurally different so won't show up on urine tests .

Effects

Short-term effects

Low to moderate doses

Benzodiazepines are prescribed for relaxation, calmness, and relief from anxiety and tension. In some cases side-effects will occur; these vary widely depending on the type of benzodiazepine, the dose, and the person , . They can include -

• impaired motor coordination,
• drowsiness,
• lethargy,
• fatigue,
• impaired thinking and memory,
• confusion,
• depression,
• altered vision,
• slurred speech,
• stuttering,
• vertigo,
• tremors,
• respiratory depression,
• nausea,
• constipation,
• dry mouth,
• abdominal discomfort,
• loss of appetite,
• vomiting,
• diarrhoea .

High doses

At high doses benzodiazepines can cause extreme drowsiness. In addition to the adverse effects listed above, the following are also observed -

• slowed reflexes,
• mood swings,
• hostile and erratic behaviour,
• euphoria .

Long-term effects

Some benzodiazepines are eliminated from the body slowly. Thus, ingesting multiple doses over long periods of time can lead to significant accumulation in fatty tissues. The symptoms of over-sedation may not appear for a few days , . Some include -

• impaired thinking,
• impaired memory,
• impaired judgment,
• disorientation,
• confusion,
• slurred speech,
• muscle weakness,
• lack of coordination .
• anxiety,
• depression,
• irritability,
• paranoia,
• aggression,
• personality change,
• weakness,
• lethargy,
• lack of motivation,
• drowsiness,
• sleepiness,
• fatigue,
• difficulty sleeping,
• disturbing dreams,
• headaches,
• nausea,
• skin rashes,
• weight gain,
• addiction .

Physical effects

• amnesia,
• disinhibition,
• dizziness,
• delusions of sobriety,
• dream potentiation,
• information processing suppression,
• motor control loss,
• muscle relaxation,
• physical euphoria,
• thought deceleration,
• seizure suppression,
• sedation .

Cognitive effects

• anxiety suppression,
• amnesia,
• compulsive redosing,
• disinhibition,
• information processing suppression,
• thought deceleration,
• emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics.
• delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages .

Adverse effects

• drowsiness,
• dizziness,
• decreased alertness and concentration,
• lack of coordination,
• decreased libido,
• erection problems,
• depression,
• disinhibition,
• hypotension,
• suppressed breathing,
• nausea,
• changes in appetite,
• blurred vision,
• confusion,
• euphoria,
• depersonalisation,
• nightmares .

Injection effects

Injecting benzodiazepines may also cause -

• vein damage,
• vein scarring,
• infection, including hepatitis B, hepatitis C, HIV and AIDS,
• DVT and clots causing loss of limbs, damage to organs, stroke and possibly death .

Injecting drugs repeatedly and sharing injecting equipment with other people increases the risk of experiencing these effects , .

Side-effects

Side-effects of benzodiazepine usage may include -

• drowsiness,
• confusion,
• dizziness,
• trembling,
• impaired coordination,
• vision problems,
• grogginess,
• feelings of depression,
• headache .

Tolerance

Tolerance to certain benzodiazepines occurs most often in those who have used for 6 months or more. Doctors counteract the effects of tolerance by increasing dosage in small increments or by adding another benzodiazepine to the prescription. Users most often develop tolerance to the milder effects of the drug, such as sedation and impairment of motor coordination. A fair amount of cross-tolerance exists between benzodiazepines and other depressants such as alcohol and barbiturates, thus users may not feel the effects of these drugs as potently as they would otherwise , .

Overdose

If someone takes an overdose of a benzodiazepine, they can suffer unpleasant and potentially harmful effects . Overdoses can cause -

• confusion,
• slurring,
• sleepiness,
• loss of coordination,
• collapse ,
• drowsiness,
• shallow respiration,
• clammy skin,
• dilated pupils,
• weak and rapid pulse,
• confusion,
• coma,
• possible death .

If someone has taken enough to become unconscious, there is a risk of -

• vomiting,
• inhaling vomit,
• choking on vomit .

all of which can potentially be fatal, and breathing can sometimes be depressed, especially in children. However, lasting harm or death from an overdose is very rare.

The danger of severe harm and death is very much greater if a benzodiazepine is taken with other sedative drugs such as alcohol, heroin or GHB. In these combinations, breathing can be depressed and stopped.

Emergency medical assistance should be sought when someone becomes unresponsive after taking drugs .

There is a low risk of fatal overdose when benzodiazepines are used on their own. They have a very high therapeutic index, and while there's a risk of unconsciousness or possible coma, the risk of death is low. This risk is raised through ignorance as to the strength of various tablets.

However, in combination with other drugs, especially alcohol and opiates, the risk of fatal overdose is far higher. A large number of dependent drinkers and people on opiate substitution therapy are also prescribed diazepam, increasing risk of dangerous polydrug use .

Benzodiazepine overdose is rarely fatal unless the drugs are mixed with barbiturates, opioids, alcohol, or tricyclic antidepressants.

The most common symptoms of benzodiazepine overdose are CNS depression and intoxication with impaired balance and movement control and slurred speech.

Flumazenil can be used as an antidote, but more often than not, the patient is simply observed and supported until the body has naturally cleared the drug .

Risks

When tablets are crushed for injection, this brings with it a range of associated health risks. Of specific concern were Temazepam Capsules. These capsules were originally introduced as a response to growing concern over Temazepam tablets being crushed for injection. The capsules contained a viscous jelly that was intended to discourage injecting. However, users found that heating the jelly made it become liquid, and so injected it. However, at lower temperature, such as at body temperature, the gel solidifies, and a large number of gruesome injecting injuries were reported. Gel capsules have not been legitimately available in the UK for over ten years .

Short-term

• tolerance,
• accidents,
• potential for overdose if combined with alcohol .

Long-term

• dependence,
• agoraphobia,
• panic attacks,
• severe anxiety .

Purity

Assuming that the pills are correctly identified and genuine, quality is assured. However, it is difficult to correctly identify all of the drugs in this family by eye, let alone assay the strength, so mistakes in strength and name are frequent amongst those purchasing outside medical spheres.

With an increasing number of imported, fake, unlicensed and novel products entering the market, the risks with non-pharmacy products will increase. Products could contain something stronger, weaker or different .

Addiction

Signs of drug addiction may include -

• drug-seeking behaviours (obtaining the drug from multiple doctors, illegally obtaining the drug),
• cravings for the drug,
• preoccupation with obtaining the drug,
• misusing the drug for intoxication or pleasure,
• dependence and withdrawal upon stopping the drug,
• interference with normal life functions (decreased work productivity, decreased motivation),
• relationship problems,
• legal issues,
• continued use despite negative consequences .

Dangerous interactions

All benzodiazepines cause excessive sedation when combined with other medications that slow the brain's processes (for example, alcohol, barbiturates, narcotics, and tranquilizers). The elimination of some benzodiazepines (for example, alprazolam [Xanax] and diazepam [Valium]) is reduced by drugs that slow elimination of drugs in the liver (for example, ketoconazole [Nizoral, Xolegel], valproic acid [Depakene, Stavzor], cimetidine [Tagamet], and fluoxetine [Prozac]). Reduced elimination may result in increased blood concentrations and side effects from the affected benzodiazepines. Antacids may reduce the rate of absorption of benzodiazepines from the intestine. Separating the administration of antacids and benzodiazepines by several hours may prevent this interaction .

Withdrawal

To ease the symptoms of withdrawal, doctors recommend that users gradually reduce the amount of medication ingested until the dose is low enough that the individual will not feel discomfort. Withdrawal symptoms are most severe when a high dose of either a short-acting or intermediate-acting benzodiazepine is abruptly discontinued , .

Giving up benzodiazepines after using them for a long time is challenging because the body has to get used to functioning without them. This is why it's important to seek advice from a health professional when planning to stop taking benzodiazepines.

Withdrawal symptoms vary from person to person and are different depending on the type of benzodiazepine being taken . Symptoms can last from a few weeks to a year and can include -

• headaches,
• aching muscles,
• twitching muscles,
• dizziness,
• tremors,
• nausea,
• vomiting,
• stomach pains,
• bizarre dreams,
• difficulty sleeping,
• fatigue,
• poor concentration,
• anxiety,
• irritability,
• altered perception,
• heightening of senses,
• delusions,
• hallucinations,
• paranoia,
• seizures , ,
• tremors,
• agitation,
• fearfulness,
• sweating,
• depersonalisation,
• derealisation,
• hypersensitivity to stimuli,
• depression,
• suicidal behaviour,
• psychosis,
• seizures,
• delirium tremens .

Drug testing

If you try to estimate how long benzodiazepines are detectable in the body you have to consider many variables, including which kind drug test is being used. Benzodiazepines - also known as Ativan, Halcion. Librium - can be detected for a shorter time with some tests, but can be 'visible' for up to three months in other tests.

The timetable for detecting benzodiazepines in the system is also dependent upon each individual's metabolism, body mass, age, hydration level, physical activity, health conditions and other factors, making it almost impossible to determine an exact time benzodiazepines will show up on a drug test.

The most significant factor influencing how long a benzodiazepine will be detected involves the elimination half-life of the particular benzodiazepine, which can vary greatly. For example, midazolam's (Halcion) half-life is quite short, and diazepam's (Valium) very long.

The following is an estimated range of times, or detection windows, during which benzodiazepines can be detected by various testing methods .

How long do benzodiazepines stay in urine?

Benzodiazepines can be detected in a urine test for up to 1 - 6 weeks .

How long do benzodiazepines remain in the blood?

Blood tests for benzodiazepines can detect the drugs for up to 6 - 48 hours .

How long can benzodiazepines be detected in saliva?

A saliva test can detect benzodiazepines for 1 - 10 days .

How long do benzodiazepines remain in hair?

Benzodiazepines, like many other drugs, can be detected with a hair follicle drug test for up to 90 days .

Mixing with other drugs

The effects of taking benzodiazepines with other drugs can be unpredictable and dangerous, and could cause -

• alcohol or opiates (such as heroin) - breathing difficulties, an increased risk of overdose and death .

The use of benzodiazepines to help with the 'come down' effects of stimulant drugs (such as amphetamines or ecstasy) may result in a cycle of dependence on both types of drug .

Taking benzodiazepines with depressant drugs increases the risk of depressing breathing. Additionally, the effects of benzodiazepines may be masked if taken with a stimulant, which can lead to an overdose if a lot of the drug is taken and then the stimulant wears off. Certain medications (e.g. some antidepressants) may also interact with benzodiazepines to increase sedative effects .

Harm reduction

• The effect of slowing reactions and making people drowsy can make accidents more likely. It can be dangerous to drive while on tranquillisers.
• As with all drugs it is best to take benzodiazepines with people you trust rather than on your own and to start with a small dose and wait.
• Alcohol can interact with benzodiazepines so is best avoided, as is using different types of benzodiazepines together.
• Crushing down tranquillisers in a solution for injection is very dangerous as the tablets often contain chalk which can lead to collapsed veins.
• It is best not to take benzodiazepines for more than 4 weeks due to the tolerance and dependence that can develop.
• Benzodiazepines should never be stopped suddenly. Always reduce their use gradually with your doctor's supervision (cite:0409).
• Alcohol can interact negatively with benzodiazepines, so it's not a good idea to drink while you're taking them.
• Benzodiazepines can also interact with one another, so it's not a good idea to take a benzodiazepine if you are already taking another. If in doubt, check with a doctor.
• If you've been prescribed a benzodiazepine and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor - don't just start increasing your dose yourself.
• Don't suddenly stop taking them, or you may start to experience symptoms of withdrawal - these can range from a return of your original symptoms (possibly even worse than before) to totally new symptoms.
• If you have become addicted to a benzodiazepine, the symptoms of abruptly stopping are likely to be even worse - it's important to get proper medical advice on how to reduce your intake slowly.
• It's also possible to become psychologically dependent on the drug (feeling like you need it all the time) - if you think this is happening, see your doctor as soon as possible, but don't suddenly stop taking it .

Paraphernalia

if tablets are crushed and injected: needles & syringes, water, matches or lighter, spoon, tourniquet .

History

Benzodiazepine development began in the 1950's following work carried out by the Polish chemist Dr. Leo Sternbach who at the time was working for the Swiss pharmaceutical company Hoffmann-La Roche.

In 1957, Sternbach tested a chemical initially thought to be pharmaceutically inactive. Surprisingly, it was found to be active against the effects of the poison strychnine while also possessing sedative and hypnotic (sleep-inducing) properties. This drug - chlordiazepoxide (Librium) went on to become the first benzodiazepine drug and was launched in 1960. By 1963, Hoffmann-La Roche had also developed and marketed the second member of the benzodiazepine drug class, diazepam which went on to achieve rapid success partly due to it being more potent than chlordiazepoxide. Compared to their previously popular predecessors (the barbiturate drugs), diazepam and other benzodiazepines offered an improved safety profile which also contributed to their popularity.

It was only after the launch of a third Hoffmann-La Roche benzodiazepine, nitrazepam (Mogadon) that different pharmaceutical companies began to develop and launch their own products. That said, of the 17 different benzodiazepines launched in the UK between 1960 and 1983, 6 of those were developed by Hoffmann-La Roche.

The 1960's and 1970's saw a rapid increase in overall benzodiazepine use - peaking in the United States during 1975 with 10% of all prescriptions issued containing a benzodiazepine. This was followed by a 6-year decline in sales until 1981 at which point a steady increase began.

Significant numbers of dependency cases involving benzodiazepines by themselves or in combination with other drugs such as opioids and alcohol were being reported as early as the 1970's, though a lack of consensus amongst medical professionals on the subject meant that no significant action was taken at the time to regulate supply more tightly and reduce the harm caused by such use.

During the 1980's, a significantly-harmful form of benzodiazepine abuse emerged in the UK involving temazepam. At the time, it was available in a capsule filled with liquid drug, commonly known as 'jellies' or 'jelly'. Many users began to extract this liquid and inject it intravenously. Unlike the overall problem of benzodiazepine abuse, this problem was quickly addressed by reformulating temazepam into a completely solid form.

Given the years during which benzodiazepines were more extensively supplied, combined with medical improvements increasing life expectancy, a growing and significant proportion of people with a benzodiazepine dependency can be found amongst the elderly .

Tranquillisers were first manufactured in the 1960's as non-addictive drugs which could be used to treat anxiety and insomnia. They were developed as a safer alternative to barbiturates which had proven to be addictive and could be highly dangerous in overdose.

Although many people, particularly women, suffered side-effects and dependence, the prescribing of tranquillisers continued to grow for over 20 years. It was not until the late 1970's that these problems were openly acknowledged. Prescriptions for tranquillisers fell from just over 30 million in 1979 to around 11 million in 2012.

Benzodiazepines have a long history of recreational use. They are taken for their relaxing and sedating properties .

During the 1930's, Leo Sternback discovered benzodiazepines while working for the Hoffman-LaRoche Company. However, the first benzodiazepine was not introduced to the general public until 1957, when Hoffman launched Librium©, which is used primarily to relieve anxiety . Abuse of benzodiazepines was not specifically addressed until the 1980s, when they became among the most prescribed medications in America .

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